National Institute Of Biomedical Imaging And Bioengineering

National Institute Of Biomedical Imaging AndBioengineering

The following abstracts of diagnostic radiology research and training grants funded by the National Institutes of Health (NIH)were awarded to principal investigators (PIs) whose primary appointments are in medical school departments of radiology.These abstracts are listed on the NIH Web page (http://www-commons.cit.nih.gov/crisp/) and are printed here verbatim.

The grant identification number (eg, 1R01AI12345-01) contains a three-digit activity code (in the previous example, R01) thatidentifies a specific category of extramural activity. All current NIH activity code titles and definitions can be obtained at theNIH Web page http://silk.nih.gov/silk/brownbooks/actcod.

IRG (Internal Review Group) refers to the study section that reviewed the application. ICD (Institute, Center, Division) refersto the NIH funding source.

The abstracts of the funded grants are printed alphabetically by author according to the funding institute or center.

NOVEL METHODOLOGY FOR STUDINGOXIDATIVE METABOLISM

Grant Number: 5R01EB004349-03

Reddy, Ravinder

Abstract: Description (provided by applicant): Oxygen

consumption provides vital information about neuronal

activity. Neurological disorders such as Alzheimer’s disease,

Parkinson’s disease, and schizophrenia are associated with

hampered enzymatic activity that catalyzes the reaction of

oxidative metabolism. Oxygen consumption also has the

potential for detecting regions of viable tissue following

cerebral ischemia. Quantitative mapping of cerebral oxygen

consumption contributes to the better understanding of the

patho-physiology of several neurological disorders. A

current method for such measurements is positron emission

tomography (PET), which provides a low-resolution image

and involves radioactive isotopes. Current 17O magnetic

resonance imaging (MRI) based methods, have limitations

such as low sensitivity and requirement of invasive proce-

dure and requirement of ultra-high magnetic fields. These

limitations, coupled with the high cost of 17O2 gas, limit the

applicability of direct 17O MRI methods to small animal

studies. Consequently, there are no non-invasive methods for

measuring oxygen consumption in humans in vivo combin-

ing safety with high spatial and temporal resolution. This

proposal deals with the development of an integrated

approach that combines an efficient 17O2 gas delivery

system with improved, noninvasive, MRI strategies for

computing cerebral metabolic rate of oxygen consumption

e118

(CMRO2). Specifically, an efficient 17O2 gas delivery sys-

tem, that reduces the 17O2 gas requirement by an order of

magnitude will be designed and optimized for use on large

animals and in humans. Efficacy of this system will be tested

on a swine model. MRI methods will be designed to mea-

sure arterial input function of metabolically produced water

(mpH217O) and cerebral blood flow. Finally, the above-

mentioned system and MRI techniques will be integrated

into an improved MRI strategy for measuring mpH217O

to compute CMRO2 in the brain in vivo. Once the aims are

accomplished, a noninvasive tool will become available to

measure CMRO2 with high spatial resolution, which can

be immediately extended to in vivo human studies. This

approach will have substantial impact on the both scientific

and clinical studies of neurological disorders and in the

development and evaluation of novel therapies.

Public Health Relevance: This Public Health Relevance is not

available.

Thesaurus Terms: Aerobiosis, brain metabolism, oxygen

consumption, technology /technique development brain

disorder diagnosis, brain imaging /visualization /scanning,

catalyst, cerebellum, enzyme activity, noninvasive diagnosis,

oxygen transport magnetic resonance imaging, oximetry,

swine

Institution: University Of Pennsylvania

3451 Walnut Street

Philadelphia, PA 19104

Fiscal Year: 2007

Department: Radiology

http://www-commons.cit.nih.gov/crisp/

http://silk.nih.gov/silk/brownbooks/actcod

Academic Radiology, Vol 16, No 7, July 2009

Project Start: 10-Feb-2005

Project End: 31-Jan-2009

ICD: National Institute Of Biomedical

Imaging And Bioengineering

IRG: MEDI

MODIFIED ELLIPTICAL CENTRIC VIEWORDERS FOR IMPROVED REAL-TIME MRA


Riederer, Stephen J.

Abstract: Description (provided by applicant): The broad,

long-term objective of this work is to develop novel, time-

efficient methods for MR data acquisition and corresponding

real-time signal processing techniques to allow formation of

MR images which portray the cardiovascular system with

high-spatial resolution. This is significant due to the high

incidence of cardiovascular disease. Specific aims to be

studied in this work are: 1. Modified Elliptical Centric (EC)

Acquisition Techniques. The EC view order will be com-

bined with projection reconstruction (PR) k-space sampling

to exploit the intrinsic advantages of both approaches. Vari-

ants of the EC-PR technique will be developed to provide: (i)

improved resolution for given time using 2D homodyne

(HD) reconstruction; (ii) time-resolved studies with frame

rates as high as 2 Hz; (iii) compatibility with parallel imaging

methods such as SENSE for 4-fold reduction in scan time;

and (iv) compatibility with a combination of SENSE and HD

reconstruction for 6-fold scan time reduction for given reso-

lution. The new methods will be applied to contrast-enhanced

as well as non-contrast-enhanced MRA studies. 2. Real-Time

Bolus Detection and Tracking. Means will be developed to

detect and track contrast bolus transit in real time in a totally

automated way as it moves through the vasculature over an

extended field of view. This information will allow the gen-

eration of patient-specific bolus velocity profiles which can

guide the MR angiographic pulse sequence and control table

velocity and optimize spatial resolution on a patient- specific

basis. 3. The Comprehensive Neurovascular Examination.

The new acquisition and real-time computation techniques of

Aims 1 and 2 will be integrated to provide a comprehensive

angiogram of the aortic arch and great vessels, the carotid

bifurcations, the intracranial arteries, and the draining veins

of the brain following a single injection of contrast. Modest

table motion during the exam will permit imaging of the

extended FOV.

Public Health Relevance: This Public Health Relevance is

not available.

Thesaurus Terms: Brain, reduction angiography, artery,

cardiovascular system, experience, neck, performance,

physics, suppression, vein, volunteer clinical research

Institution: Mayo Clinic Coll Of Medicine,

Rochester

200 1st St SW

Rochester, MN 55905

Fiscal Year: 2007

Department:

Project Start: 01-Aug-1984

Project End: 31-Mar-2010



IRG: BMIT

IMAGING PANCREATIC B-CELL FUNCTIONBY MAGNETIC RESONANCE


Roman, Brian B.

Abstract: Description (provided by applicant): The use of

MRI imaging as a non-invasive tool to assess encapsulated

pancreatic beta cell viability is proposed. The immunoiso-

lation of transplanted islets has emerged as a promising

method of treating Type I Diabetes, and is potentially the

only strategy that provides both the safety of avoiding

immunosuppressant drugs and the effectiveness of mea-

suring blood glucose as accurately as only living cells can.

Since the device functions as an implantable homeostatic

sensor-release system, it is fundamental for the encapsu-

lated cells to be able to respond promptly to fluctuations in

glucose concentrations of the interstitial fluid in order to

retain a physiologic dynamic response. Currently, efficacy

of the biocapsule is assessed indirectly by measuring serum

glucose levels, and although insulin secretion may remain

constant, levels of ATP, glucose consumption and lactate

production may change, and may be indicators of irre-

versible damage to the encapsulated cells. In this proposal,

NMR spectroscopy and microimaging will be used to an-

alyze the physical and physiological status of the pancreatic

beta cells. A novel MR imaging method is proposed to

non-invasively assess cell activation. Pancreatic b-cells

activated by increased glucose levels induce Ca2+ uptake

through L-type voltage-gated Ca2+ channels. Mn2+ acts as

a Ca2+ analog and enters cells through L-type voltage

gated channels. Additionally, Mn2+ is a MR relaxation

agent and reduces the T1 of water, resulting in a change in

image contrast. Therefore beta cells activated by increased

e119


glucose in the presence of Mn2+ will demonstrate a change

in MR signal intensity compared to non-activated cells.

Using the high spatial resolution abilities of MRI, this

approach will allow us to directly image beta cell function

and viability. Simultaneously it will be possible to apply

localized spectroscopic techniques to construct metabolic

profiles of activated versus non-activated regions. In con-

cert, these techniques will provide means to understand

beta cell function, factors influencing successful islet

transplantation, and the further development of encapsu-

lated pancreatic beta cells necessary for a bioartificial

pancreas.


not available.

Thesaurus Terms: Blood glucose, diagnosis design

/evaluation, magnetic resonance imaging, metabolism dis-

order diagnosis, pancreas imaging /visualization, pancreatic

islet biosensor device, calcium channel, calcium transporting

ATPase, glucose metabolism, insulin dependent diabetes

mellitus, manganese, osmotic pressure, voltage gated chan-

nel bioimaging /biomedical imaging, laboratory rat

Institution: University Of Chicago

5801 S Ellis Ave

Chicago, IL 60637

Fiscal Year: 2007


Project Start: 30-Sep-2003

Project End: 31-Jul-2009



IRG: ZRG1

REDUCED DOSE NEURO CT PERFUSIONUSING HYPR


Rowley, Howard A.

Abstract: Description (provided by applicant): Two of the

present limitations associated with X-ray CT perfusion are

X-ray dose and the use of iodinated contrast materials. In

the work proposed here we intend to test the hypotheses

that CT perfusion can be done using one tenth of the

conventional X-ray dose per time frame using iodinated

contrast material. Our group has recently developed

a unique data acquisition and reconstruction strategy called

HYPR (HighlY constrained back PRojection) that exploits

the redundancy of information in a temporal series of im-

ages. Basically, a composite image is formed from all

e120

acquired projections. The composite image is then used to

constrain the backprojection of the data acquired in indi-

vidual time frames. The method has provided acquisition

acceleration factors as high as several hundred in MR an-

giography but acceleration is reduced in other applications

for which greater numbers of projections are required to

characterize the time frames. The degree of acceleration

depends on the sparsity of the data in the composite image.

We propose to extend the HYPR method to X-ray CT

where the use of a reduced number of projections per time

frame results in reduced x-ray dose. The SNR characteris-

tics of HYPR are such that the SNR generated by all

projections in the temporal series feeds back into the SNR

of the individual time frames. This represents a completely

new SNR behavior in which SNR of individual time

frames is proportional to the square root of overall scan

time rather than the square root of the frame time. The

investigation involving iodinated contrast material will

consist of simulations, phantom studies, animal studies and

clinical evaluations. We also propose to investigate to

perform simulations, phantom studies and animal studies to

investigate the feasibility of performing perfusion studies at

current or possibly reduced dose levels using gadolinium

contrast materials.


not available.

Thesaurus Terms: X ray, material, perfusion angiography,

back, behavior, gadolinium, root, sectioning clinical research

Institution: University Of Wisconsin Madison

21 N. Park

Street, Suite 6401

Madison, WI 537151218

Fiscal Year: 2008



Project End: 30-Jun-2010



IRG: MEDI

MICRORADIOGRAPHIC GUIDANCE OFFLOW MODIFYING STENTS


Rudin, Stephen

Abstract: Description (provided by applicant): The aim of

this project is to build a new very high spatial resolution,

rapid frame rate region of interest (ROI) x-ray detector


system, the micro-angiographic fluoroscope (MAF) and to

use it for guiding and evaluating new stents used for flow

modification in the treatment of intracranial aneurysms. The

detector due to its large adjustable gain will be capable of

acquiring 30 fps at both fluoroscopic exposures in the frac-

tional microR and higher range as well as at angiographic

exposures in the mR range. The detector will have adjustable

pixel size and be capable of pixel sizes less than 50 mu/m and

will have high-contrast spatial resolution greater than 10 lp/

mm while operating at typical angiographic kVp’s. The MAF

will have a viewing field of at least 5 cm diameter sufficient

for viewing small regions where interventions and in partic-

ular flow modifying interventions are occurring. The MAF

will be compatible with existing commercial angiographic x-

ray sources and be mounted in such a way as to be interposed

between the x-ray image intensifier, X/I, of the commercial

system and the phantom, animal, or patient so that the MAF

can be used when its high resolution ROI capabilities are

needed, usually at critical times during interventional

procedures. Additionally, the MAF will be used for cone-

beam rotational microangiography and micro-computed to-

mography (CT) for determining vessel lumens needed for

accurate flow assessment. Also, the new imaging capability

for accurate localization will allow the development and

implementation of new devices: asymmetric, variable po-

rosity stents for treatment of cerebral aneurysms by modify-

ing aneurysm blood flow characteristics. To optimize the new

stent design, flow reduction in aneurysms needed to induce

thrombosis will be explored. Also details of flow and flow

modification will be investigated using advanced theoretical

and experimental methods. Finally clinical application of the

high-resolution microfluoroscopic detector will be used to

evaluate the use of stents for flow modification in the cere-

brovasculature of human patients.


not available.

Thesaurus Terms: X ray, biomedical equipment

development, blood vessel prosthesis, microradiography

aneurysm, cerebrovascular imaging /visualization angiogra-

phy, bioengineering /biomedical engineering, bioimaging

/biomedical imaging, clinical research, computed axial to-

mography, dog, fluoroscopy, human subject

Institution: State University Of New York

At Buffalo

Sponsored Projects Services

Buffalo, NY 14260

Fiscal Year: 2007

Department: RADIOLOGY

Project Start: 20-SEP-2003

Project End: 31-JUL-2009



IRG: ZRG1

COMPUTER-AIDED DETECTION FOR MRIBREAST SCREENING

Grant Number: 5K25EB005077-05

Schabel, Matthias

Abstract: Description (provided by applicant): We propose

to design, develop and implement a computer-aided detec-

tion system for integrating multiple magnetic resonance im-

aging (MRI) modalities for EARLY DETECTION OF

BREAST CANCER IN HIGH RISK PATIENTS, using

structural, dynamic contrast enhanced (DCE), and diffusion-

weighted (DW) MRI, and magnetic resonance spectroscopy

(MRS). Incorporation of morphological and parametric in-

formation from structural and DCE MRI data leads to notable

improvements in both sensitivity and specificity. However,

sensitivity remains suboptimal, particularly for screening

purposes. By incorporating additional contrast information

derived from DW images and MRS data, further improve-

ments in detection accuracy are expected. A hierarchical set

of algorithms will be implemented, using a combination of

static feature descriptors, neural networks, and decision tree

analysis to integrate the multimodality data. Early detection

of breast cancer is an extremely active area of research,

driven by the mediocrity of current mammographic screening

methodologies and the consequent expense and inconve-

nience of unnecessary biopsies of breast lesions ultimately

identified as benign. Dr. Schabel will apply his strong back-

ground in computational simulation and modeling, spectro-

scopic data analysis, and image processing toward the

detection system described above while developing MRI

expertise. Concomitantly he will test and develop appropriate

methodologies for application of our new Siemens 3 T MRI

system. With the significant benefits in signal-to-noise to be

gained from using the 3 T system, it is likely that this

will develop into a fertile area for future work in screening

and early detection. The University of Utah provides a unique

constellation of resources for this project. UCAIR has faculty

and staff with extensive practical experience with all pro-

posed MRI modalities, and is equipped with cutting edge

MRI instrumentation. A group of high-risk breast cancer

patients willing to participate in clinical trials is already in

place at the Huntsman Cancer Institute, forming a body of

e121


prospective participants for the clinical work proposed. Fi-

nally, the close participation of clinical radiologists with Dr.

Schabel will significantly facilitate the algorithmic work by

providing the knowledge and expertise in interpreting ra-

diologic images against which algorithms will be tested.


not available.

Thesaurus Terms: Breast neoplasm /cancer diagnosis,

computer assisted diagnosis, computer system design

/evaluation, diagnosis design /evaluation, early diagnosis,

magnetic resonance imaging clinical trial, diagnosis quality

/standard, image enhancement, image processing, time re-

solved data, women’s health bioimaging /biomedical imag-

ing, clinical research, computer program /software, human

subject, mathematical model

Institution: University Of Utah

75 South 2000 East

Salt Lake

City, UT 84112

Fiscal Year: 2008



Project End: 31-Aug-2009



IRG: NCI

RESEARCH TRACK RADIOLOGYRESIDENCY

Grant Number: 5T32EB004311-04

Schnall, Mitchell D.

Abstract: Description (provided by applicant): The Depart-

ment of Radiology at the University of Pennsylvania pro-

poses an innovative training program with the aim of

developing imaging clinician scientists. The growing role of

imaging in clinical care and biomedical research has resulted

in an acute need for imaging-based clinician scientists. There

is a talented pool of resident applicants to academic radiology

residency programs across the US, with only a small fraction

pursuing academic careers. Even a smaller fraction of

trainees are developed into clinician scientists. The training

program described in this proposal builds on the excellent

clinical training programs and the large research infrastruc-

ture within Penn’s Radiology department in order to develop

a residency track designed for trainees interested in careers as

imaging scientists. The research track includes 2 years of

research training, the first during residency and a second as

e122

part of a fellowship. Clinical training will focus on areas of

specific interest to the trainee in addition to meeting the re-

quirement for board certification. The research years are

separated by the PGY 5 clinical year during which trainees

will prepare for and complete the board examination in Di-

agnostic Radiology. In addition to the research percepter-

ships, the program includes didactic courses in imaging

technology, basic biology, biostatistics and clinical research

design. Research seminars and close mentoring also repre-

sent significant components of the program. It is believed that

an integrated training program offered throughout the Na-

tional Residents Matching program will offer an opportunity

to engage residents early in their training resulting in com-

mitted well-trained imaging clinical scientists, meeting a na-

tional need.


not available.

Thesaurus Terms: There are no thesaurus terms on file for

this project.


3451 Walnut Street


Fiscal Year: 2008


Project Start: 01-May-2005

Project End: 30-Apr-2010



IRG: ZEB1

SIMULATION TOOLS FOR DYNAMIC CT


Segars, William P.

Abstract: Description (provided by applicant): Simulation

is a powerful tool for characterizing, evaluating, and opti-

mizing medical imaging systems and mage processing and

reconstruction methods. The two major components of sim-

ulation are: (1) a realistic model of the human anatomy and

physiological functions, and (2) ability to generate accurate

image data that include effects of the imaging process.

Without such, the results of the simulation may not be in-

dicative of what would occur in actual patients and would,

therefore, have limited practical value. The current four-di-

mensional (4D) NURBS-based cardiac-torso (NCAT) phan-

tom was developed to provide a realistic and flexible model

of the human anatomy and physiology and is widely used in

nuclear medicine imaging research. The phantom has the


advantage, due to its design, that its organ shapes can be

changed to ealistically model different anatomical variations

and patient motion. Although capable of being far more

realistic, the NCAT phantom was designed for low-resolu-

tion nuclear medicine imaging research, and lacks the ana-

tomical detail to be applicable to high-resolution CT. At the

same time, current phantoms used in CT lack sufficient re-

alism in depicting the complex shapes of real human organs

and the flexibility to model anatomical variations and normal

physiologic motion, deficiencies that are becoming increas-

ingly important with rapid advancements in these imaging

technologies and in the development of new applications. We

seek to fill this void by building upon the existing 4D NCAT

phantom and other simulation tools developed in our labo-

ratory. We hypothesize that the tools developed in this work

will provide simulated CT image data that accurately mimic

that obtained from actual patients (male and female) at dif-

ferent stages of development (adult and pediatric). As x-ray

CT evolves into many new applications and gains wider use,

the simulation tools developed in this work will have appli-

cations in a broad range of imaging research in developing

image acquisition strategies, image processing and recon-

struction methods, and image visualization and interpretation

techniques. Also, the tools provide the necessary foundation

to optimize clinical CT applications so as to obtain the

highest possible image quality with the minimum possible

radiation dose to the patient. Due to radiation concerns it is

impractical to optimize the large number of imaging param-

eters available in modern CT systems in human patients in

ways that are specific to clinical demands. It is equally im-

practical to perform optimizations in physical test objects that

cannot realistically duplicate the conditions seen in vivo.

Such a task can only be practically and efficiently performed

using accurate and realistic computer simulation methods,

which have not yet been developed. Our team of investigators

and consultants has extensive expertise in developing digital

phantoms, accurate models of the medical imaging process,

and 3D image reconstruction techniques and methods that are

well suited for this project.


not available.

Thesaurus Terms: Computed axial tomography, computer

simulation, computer system design /evaluation, image

enhancement, method development, model design /devel-

opment, phantom model, three dimensional imaging /to-

pography analytical method, computer program /software,

computer system hardware, heart imaging /visualization

/scanning, mathematical model, noise, pediatrics, radiation

dosage, respiratory imaging /visualization, statistics /biome-

try bioimaging /biomedical imaging, human data

Institution: Duke University

2200 W. Main St.

Durham, NC 27705

Fiscal Year: 2007

Department: RADIOLOGY

Project Start: 22-SEP-2005

Project End: 31-AUG-2009



IRG: BMIT

A CONTEXT-SENSITIVETELECONSULTATION INFRASTRUCTURE


Sinha, Usha

Abstract: Description (provided by applicant): Consultation

with appropriate specialists improves the quality of health-

care, particularly in patients with complicated cases or

chronic illnesses. And for the majority of such patients,

specialists use imaging studies (e.g., MR, CT) to objectively

document the disease process (e.g., a cancer patient on che-

motherapy). However, specialists are generally not available

in all communities, tending to be concentrated in academic/

specialty centers. Thus, to facilitate the routine use of tele-

consultations for patients when specialists are not locally

present: 1) the images captured to document the patient’s

condition must be incorporated into the medical record to

enable proper review; and 2) the remote consultant should

only receive pertinent parts of the medical record to stream-

line the consultation process. This proposal is focused on

developing and testing a "context-sensitive" telehealth in-

frastructure based on: 1) automated incorporation of clinical

context (patient presentation and referring physician hy-

pothesis) to focus the consultation process; 2) a knowledge-

base derived from data mining of natural language processing

(NLP) results, mapping patient presentation to select an ap-

propriate imaging study based on anatomical region and

imaging parameters; and 3) automated selection of key ana-

tomical structures in the acquired imaging study through the

use of a contrast-customizable atlas and rigid body/deform-

able registration algorithms. Collectively, these technologies

will allow context-sensitive, automated summarization of

medical records for telehealth in a real-world environment.

The proposed technologies will be implemented for neuro-

logical and musculoskeletal domains, two areas that are MR

e123


imaging intensive. Technical evaluation will be performed

with experts serving as the reference standard and will focus

on measuring: 1) the accuracy of the corpus based, NLP-

guided knowledge-base in selecting relevant anatomical

structures; and 2) the accuracy of anatomical structure de-

lineation using the customizable atlas registration methods.

Clinical evaluation will be conducted in a real-world tele-

consultation environment in a before/after study design using

two performance metrics: 1) the time required for consulta-

tions; and 2) the effect on the quality of the consultations.


not available.

Thesaurus Terms: Computer assisted diagnosis, computer

assisted medical decision making, computer data analysis,

computer system design /evaluation, diagnosis quality

/standard, health care quality, health care referral /consulta-

tion, image processing, telemedicine anatomy, computer as-

sisted patient care, image enhancement, musculoskeletal

disorder, nervous system disorder clinical research, computer

graphics /printing, human data, magnetic resonance imaging,

statistics /biometry

Institution: University Of California Los Angeles

Office Of Research Administration

Los Angeles, CA 90095

Fiscal Year: 2007

Department: Radiology (Radiological Sciences)





IRG: ZRG1

HIGH-PERFORMANCE HIGH-FIELDPARALLEL MRI


Sodickson, Daniel K.

Abstract: Description (provided by applicant): Clinical and

research applications of magnetic resonance imaging con-

tinue to demand improvements in spatial and temporal res-

olution. Two of the most promising means of exceeding

existing limits on spatial and temporal resolution include the

use of high magnetic field strengths, on the one hand, and the

use of radiofrequency (RF) coil arrays for accelerated parallel

imaging, on the other. Particular synergies are expected for

combinations of these approaches. Shortened acquisition

times resulting from parallel imaging may be used to over-

come some of the challenges associated with high-field

e124

studies, including susceptibility artifacts and specific ab-

sorption ratio (SAR) constraints. Meanwhile, increased spin

polarization at high field strength results in increased signal

to noise ratio (SNR), which can enable higher accelerations

than would be possible at lower fields. Additional synergies

have recently been predicted. Calculations of ultimate in-

trinsic SNR show marked improvements in achievable par-

allel imaging performance with increasing field strength,

above and beyond the effects of increased spin polarization.

These improvements have been traced to the reduced RF

wavelength and improved RF focusing capability at high

field strength. Access to the full benefits of this synergy be-

tween parallel imaging and high field strength will require

changes in some of the traditional paradigms for coil array

and RF system design. The broad goal of this proposal is to

solve the theoretical and practical issues of RF design re-

quired in order to approach the computed optimal parallel

imaging performance as a function of field strength. We

propose to evaluate the efficacy of various decoupling strat-

egies, to establish concrete benchmarks for practical coil

sizes, and to build prototype many-element arrays capable of

order-of-magnitude accelerations at 1.5 T and 3 T. In the

course of the project, we will also establish the basic princi-

ples by which these designs may be extended to higher field

strengths in order to yield still greater improvements in spa-

tial and temporal resolution. Specific the proposed research

are as follows: 1. Using 8-element test arrays, assess the

impact of inter-element decouAims ofpling strategies upon

baseline SNR, and implement the strategy that yields the best

SNR. 2. Use new 32-receiver systems scheduled to be in-

stalled at Beth Israel Deaconess Medical Center to establish

the smallest practical coil size for 32-element arrays as

a function of field strength. 3. Based on the results from

Specific Aims 1 and 2, construct 32-element arrays suitable

for two-dimensional accelerations at 1.5 T and at 3 T, re-

spectively, and perform quantitative comparisons of array

performance. 4. Use two-dimensional acceleration in com-

bination with these arrays to achieve order-of-magnitude

increases in spatial and/or temporal resolution for a set of

imaging sequences used commonly in cardiac, breast, body,

and brain imaging applications. 5. Adapt target field methods

from gradient coil design to establish robust parallel imaging

array designs that approximate the computed optimum be-

havior at higher field strength.


not available.

Thesaurus Terms: Image enhancement, magnetic resonance

imaging, technology /technique development biomedical


equipment development, magnetic field, radiowave radiation

bioimaging /biomedical imaging, clinical research, human

subject

Institution: New York

University School Of Medicine

550 1st Ave

New York, NY 10016

Fiscal Year: 2007






IRG: ZRG1

THICK SCINTILLATION DETECTOR WITHCONTINUOUS POSITIONING & DOICAPABILITY FOR PET


Surti, Suleman

Abstract: Description (provided by applicant): The long-

term objective of this work is the development of a general,

practical, PET detector that can achieve very good spatial

resolution for the imaging situation at hand without a sig-

nificant compromise in other important properties, specifi-

cally, sensitivity, and energy and timing resolutions. The

primary goal of this project is to design a thick (25-mm),

continuous detector with an independent depth-of-interac-

tion (DOI) measurement. The DOI measurement, besides

reducing parallax effect in the scanner, will enable a coarse

sampling of the 3D light spread along the depth (z) and

a fine sampling in the two transverse directions (x,y). With

such a characterization of the 3D light spread, we expect to

maintain good spatial resolution in the thick detector. The

ease of manufacture and reduced cost, improved packing

fraction, and promise of good or better energy and timing

resolution compared to pixelated detectors, makes this de-

tector design practical and high performance. The main

innovation over previously investigated continuous detec-

tors is the ability to achieve and maintain high spatial

resolution in thick detectors over most of the detector FOV,

making the detector a practical solution for PET imaging

due to its high sensitivity. The high spatial resolution of

this detector together with DOI measurement will allow the

manufacture of smaller ring diameter scanners which pro-

vides increased sensitivity, reduced cost due to less scin-

tillator used, and reduced annihilation photon non-

collinearity effect on spatial resolution. Recent work with

thin crystals suggests that it is possible to achieve very

high spatial resolution in continuous detectors. However,

since the light spread in a continuous detector is a function

of all three crystal dimensions and leads to degeneracies in

the accuracy of the positioning algorithm, it is almost im-

possible to maintain this spatial resolution over the entire

field-of-view (FOV) of detectors that are thick enough to

provide the high sensitivity needed for PET. In this work

we will establish the use of a lightguide and independent

DOI measurement to de-couple the 3D nature of the light

spread in a thick detector, thus improving transverse reso-

lution. This work will result in a splitting of the detector

into several interaction depth levels, with good transverse

resolution within each level. Also, we will investigate

through Monte Carlo the ability to match the measured

light spread in these detectors. This Monte Carlo will be

used to describe the full 3D light spread in the detector that

can further improve spatial resolution, and also lead to an

easier calibration procedure for the detector. Finally, dif-

ferent crystal materials and surface finishes, as well as

varying light sampling techniques, will be investigated

through simulations and measurements to achieve good

spatial resolution while maintaining the energy and timing

resolution in these detectors. Clinically for human imaging,

limited spatial resolution of current generation of PET

scanners leads to partial volume effects in the measured

uptake of small lesions. By improving the spatial resolution

to the best possible limit, the overall efficacy of clinical

diagnosis will be significantly improved and small lesions

that often represent the initial stage of cancer will be

characterized early enough to guide the therapy. Hence,

thick continuous detectors have the potential to signifi-

cantly impact the clinical imaging situation and the resul-

tant patient treatment.


not available.


this project.


3451 Walnut Street


Fiscal Year: 2008






IRG: ZRG1

e125


IMPROVED MRI TECHNIQUES FORMEASUREMENT OF ABSOLUTETEMPERATURE DISTRIBUTIONS

Grant Number: 5F31EB007892-02

Todd, Nicholas E.

Abstract: Description (provided by applicant): The goal of

this research project is to develop and implement an MRI-

based technique that creates accurate, real-time temperature

maps of tissue that are vital to thermal therapy procedures.

This research is a vital part of making thermal therapies

clinically viable. For thermal therapy procedures to be safe,

effective and time-efficient, the tissue in the region of interest

must be monitored for temperature changes throughout the

treatment. The goal of this research project is to develop and

implement 3D magnetic resonance imaging (MRI) tempera-

ture measurement techniques to create accurate, robust, real-

time temperature maps that can be used to monitor tissue

heating during thermal therapy treatments. To achieve this

goal, the research will focus on three areas: 1) develop im-

proved temperature measurement techniques and demon-

strate they are capable of measuring temperature distributions

in tissue; 2) reduce temperature measurement errors that are

due to motion; 3) investigate techniques to increase acquisi-

tion speed. 1) Three pulse sequences are currently being in-

vestigated as possible options to be used in conjunction with,

or as an alternative to, the widely popular, but error prone,

proton resonance frequency shift (PRFS) technique. A

chemical shift spectroscopy pulse sequence, and two 3D

single-shot diffusion weighted pulse sequence are all cur-

rently operational. Their imaging parameters will be opti-

mized for temperature measurement and they will be tested in

heating experiments on ex vivo and in vivo tissue samples. 2)

The self referencing capability of the spectroscopic pulse

sequence can potentially be used to reduce errors from mo-

tion. In ex vivo and in vivo tissue studies, we will test the

ability of the spectroscopic sequence to use the fat signal to

reduce both motion induced susceptibility errors and motion

induced registration errors. 3) Two techniques will be in-

vestigated for improving the temporal resolution of the scans.

The use of parallel imaging along with reconstruction algo-

rithms such as GRAPPA can be applied to any pulse se-

quence to decrease the scan time. A temporally constrained

reconstruction algorithm has been shown to be capable of

reducing scan time and can also be implemented with any

pulse sequence.


not available.

e126


this project.

Institution: University Of Utah

75 South 2000 East

Salt Lake City, UT 84112

Fiscal Year: 2008



Project End: 19-Sep-2009



IRG: ZRG1

HIGH-RESOLUTION SPECT FORMOLECULAR IMAGING


Tsui, Benjamin M.

Abstract: Description (provided by applicant): The long-

term goal of this project is to develop an advanced mu/

SPECT/CT molecular imaging technology including a state-

of-the-art innovative mu/SPECT system and accurate quan-

titative pinhole and multi-pinhole SPECT imaging tech-

niques that provide ultra-high-resolution down to

approximately 0.5 mm and detection efficiency on the order

of 2 cps/mu/Ci. To evaluate the novel fSPECT/CT technol-

ogy, we propose to perform simulations as well as experi-

mental phantom and small animal imaging studies. To

respond to the main concern of the reviewers that the previ-

ous proposal was too diffuse, we have refocused the research

by redesigning the mu/SPECT system configuration with

a fixed-angled detector assembly without going through the

prototype stage, constructing the unique ‘angled detector

module assembly’ with the latest high performance but ro-

bust detector technologies, eliminating the longitudinal to-

mography study using planar multi-pinhole imaging with

standard gamma camera system, deleting two small animal

imaging studies to focus on the most important application to

imaging of plaques in mice, and switching to a simpler

transgenic mouse model with stable and unstable plaques.

Also, the proposal is strengthened by additional preliminary

data from multi-pinhole image reconstruction, Monte Carlo

simulation of pinhole SPECT data, and plaque imaging in

transgenic mice using 99mTc Hynic-Annexin V. The team of

investigators is streamlined with 2 groups of investigators

and 3 key consultants with relevant areas of expertise. The

revised specific aims are: (1) to develop a state-of-the-art

‘angled’ detector module and single and multiple pinhole

collimation and an x-ray imaging device for use in the mu/


SPECT/CT systems in Aim #5, (2) to develop simulation

software for 3D SPECT imaging that models performance

characteristics of the scintillation camera modules, design

parameters of single and multiple pinhole collimator, and the

SPECT system geometry and configuration, (3) to develop

3D quantitative SPECT image reconstruction methods for

single and multiple pinhole SPECT with correction of at-

tenuation, scatter and collimator response for accurate abso-

lute quantitation of radioactivity in vivo, (4) to develop

simple, accurate and robust calibration methods for single

and multi-pinhole SPECT systems, (5) to develop a prototype

mu/SPECT/CT system that includes two angled detector as-

semblies developed in Aim #1 and an existing mu/CT system

that will be mounted on a commercial grade CT gantry, and

(6) to evaluate the pinhole SPECT imaging techniques and

the mu/SPECT/CT system in imaging stable and vulnerable

plaques in a transgenic mouse model using 99mTc labeled

Annexin-V.


not available.

Thesaurus Terms: Biomedical equipment development,

computed axial tomography, image enhancement, image

processing, molecular biology, single photon emission

computed tomography, three dimensional imaging /topog-

raphy X ray, atherosclerotic plaque, technetium bioengi-

neering /biomedical engineering, bioimaging /biomedical

imaging, genetically modified animal, laboratory mouse,

phantom model

Institution: Johns Hopkins University

W400 Wyman Park Building

Baltimore, MD 212182680

Fiscal Year: 2007

Department: Radiology And Radiological Sciences





IRG: ZRG1

CORRECTIVE IMAGE RECONSTRUCTIONMETHODS FOR ECT


Tsui, Benjamin M.

Abstract: Description (provided by applicant): In this re-

submission of a 5-year competing renewal grant application,

we have carefully addressed the concerns raised in the pre-

vious review. The roadmap of this project from the beginning

has been and continues to be the development, optimization,

validation, and evaluation of 2D, 3D to 4D corrective image

reconstruction methods for SPECT and PET in order to

provide and demonstrate significant improvement in image

quality for clinical diagnosis. Use and development of a va-

riety of supporting methodologies, experiments and clinical

trials have been and are essential in achieving this goal. Past

accomplishments include pioneering and innovative work

notably the development of the widely popular 4D computer

generated NCAT phantom, accurate and efficient simulation

of ECT data, 2D, 3D, and 4D corrective image reconstruction

methods that have been licensed by a major commercial

vendor, and task-based optimization and evaluation methods

using populations of subjects that include anatomical and

physiological variations. Our main hypothesis in the pro-

posed project is that substantial further improvements in ECT

image quality will be obtained from the use of 3D and 4D

corrective image reconstruction methods, including correc-

tions for non-clinical factors as well as patient involuntary

motion, specifically respiratory motion. We propose to con-

tinue our ground-breaking work through further development

of the 4D NCAT phantom for more realistic modeling of

normal and abnormal respiratory anatomy and function. We

will also extend our existing corrective image reconstruction

methods from 2D and 3D to 4D with the goal of improving

the detection of abnormalities. An important innovation is the

proposed development and use of task-based evaluation

methods that use mathematical observers and populations of

phantoms that include anatomical and physiological varia-

tions that realistically model those found in clinical

data. Several important clinical ECT applications including

myocardial perfusion SPECT, oncological SPECT using

123I labeled agents and oncological lung and liver PET using

18F labeled FDG have been chosen as examples to evaluate

the clinical efficacy of the 4D corrective image reconstruction

methods. Realistic simulated imaging data from populations

of 4D NCAT phantoms with anatomical and physiological

variations, experimental data from physical phantoms, and

clinical data from patient studies will be used. Results of the

evaluation studies using simulated data from populations of

phantoms and mathematical and human observers will be

compared to those obtained using clinical data and trained

physicians. In addition to contributing to the improvement of

clinical diagnosis through the development of 4D corrective

image reconstruction methods for ECT, the proposed re-

search will make significant contributions to the under-

standing of observer performance in clinical evaluation of

e127


medical imaging systems and techniques, provide more re-

alistic simulation tools, and demonstrate their the utility as

possible replacement for costly clinical trials.The goal of the

project is to develop methods to give doctors better images of

the heart and cancers using SPECT and PET scanners. The

research makes use of state-of-the-art scientific methods to

find the best possible ways to give much clearer images than

those provided by existing methods. To make sure the new

methods are really an improvement, we will check them

carefully using computer generated images, then images

from experiments, and finally to images from approved pa-

tient studies.


not available.


this project.




Fiscal Year: 2008


Project Start: 01-Dec-1986




IRG: ZRG1

CONTINUED DEVELOPMENT, PORTING,MAINTENANCE OF 3DVIEWNIX


Udupa, Jayaram K.

Abstract: Description (provided by applicant): The broad

goal of this project is to develop, test, evaluate, maintain,

document, and distribute a comprehensive software system

for the Computer Aided Visualization and Analysis

(CAVA) of multidimensional medical images. The open

source software systems currently available for CAVA

have four key limitations: (1) They have been developed

either for mostly image processing or for mostly visuali-

zation, and very minimally for structure manipulation and

analysis. Systems encompassing all four elements of pro-

cessing in a comprehensive manner do not exist at present.

(2) Their usability by basic scientists as well as biomedical

researchers has serious limitations. (3) They have serious

speed limitations. (4) They lack interoperable, portable in-

terfaces to other software packages and peripheral hard-

ware. By utilizing a previously developed software system

e128

called 3DVIEWNIX, the aim of this project is to develop

a new open-source/conditional open-source system called

CAVA software system (CAVASS) that will effectively

overcome the above limitations. To achieve these goals, all

libraries of 3DVIEWNIX will be ported from its current

Linux/Unix environment to include also Windows and Mac

OS. For key CAVA operations that have computational

bottlenecks, parallelized implementations will be developed

so that the speed issue can be resolved in a portable

manner in multiprocessor systems. The Graphical User

Interface and the graphics interface of 3DVIEWNIX will

be updated utilizing wxWindows so as to provide a porta-

ble stereo visualization interface by employing inexpensive

hardware (such as shutter glasses) and easy means to in-

terface to other systems such as ITK, Matlab, Mathematica,

and CAD/CAM and statistical packages. CAVASS will be

developed in such a manner that it will not only provide

a rich resource of all CAVA functions but will also serve

different user groups unlike existing open-source software

systems. This will include researchers involved in the de-

velopment of the basic science and technology of CAVA,

developers of biomedical applications of CAVA, and bio-

medical end users who wish to use the software system in

clinical/biomedical research.


not available.

Thesaurus Terms: Bioimaging /biomedical imaging, com-

puter program /software, computer system design /evalua-

tion, image processing computer data analysis, informatics,

three dimensional imaging /topography


3451 Walnut Street


Fiscal Year: 2007






IRG: ZRG1

QUANTITATION OF THE BOLD EFFECT INFUNCTIONAL MRI


Van Zijl, Peter Cm.

Abstract: Description (provided by applicant): The BOLD-

fMRI approach has revolutionized assessment of brain


function. This complex effect represents MRI signal changes

that are consequential to a hemodynamic response secondary

to activation. As the BOLD response reflects the changing

oxygen extraction fraction, OEF, it allows some insight into

basic brain physiology. However, such interpretations are

confounded by multiple contributions to the effect. BOLD is

sensitive not only to intravascular oxygenation changes, but

also to extravascular effects of such changes around paren-

chyma and around veins draining from activated cortex. In

addition, BOLD is influenced by alterations in voxel com-

position due to changes in cerebral blood volume (CBV).

Contributions of these effects to the BOLD signal intensity

changes depend on magnetic field strength, voxel size, type

of MRI experiment (spin echo/gradient echo). Thus, there are

many variables and few observable parameters. In the pre-

vious period we have developed a new fMRI approach that

can add several essential observables, namely tissue frac-

tions, CBV and the tissue relaxation rates. We also re-inter-

preted the BOLD post-stimulus undershoot in terms of

continued oxygen metabolism and showed that, surprisingly,

BOLD spin-echo signals can occur in draining veins. The

ultimate goal of this proposal is to gain a complete quanti-

tative understanding of the physiological, physical, and

spatial aspects of the BOLD effect. In AIM 1 we propose

experiments to confirm the proposed oxygen-metabolism

based character of the BOLD post-stimulus undershoot and

to develop strategies to use this undershoot for fMRI voxel

selection. In AIM 2 we propose experiments that can distin-

guish intravascular, extravascular, macrovascular, and mi-

crovascular BOLD components. This data will be used to

evaluate existing extravascular BOLD theories. In AIM 3 we

measure the blood transverse relaxation rates for blood in

which the transport properties of erythrocyte water channels

are impaired by an aquaporin channel blocker. This will be

combined with our previous data without blocker to evaluate

the effect of exchange versus magnetic field gradients on the

intravascular BOLD effect. Based on our blood data acquired

in the previous grant period and our in vivo data proposed to

be acquired here, we will derive a quantitative description for

the BOLD effect that has only physiological and physical

parameters. This formalism should allow description of the

BOLD effect for all physiological perturbations.


not available.

Thesaurus Terms: Brain circulation, brain imaging

/visualization /scanning, cerebrovascular imaging /visuali-

zation, functional magnetic resonance imaging, method de-

velopment, oxygen tension, oxyhemoglobin acidity

/alkalinity, blood volume, hemoglobin bioimaging /biomed-

ical imaging, clinical research, human subject




Fiscal Year: 2007


Project Start: 01-Apr-1999




IRG: RNM

QUANTITATION OF THE BOLD EFFECT INFUNCTIONAL MRI


Van Zijl, Peter Cm.

Abstract: Description (provided by applicant): The

BOLD-fMRI approach has revolutionized assessment of

brain function. This complex effect represents MRI signal

changes that are consequential to a hemodynamic response

secondary to activation. As the BOLD response reflects the

changing oxygen extraction fraction, OEF, it allows some

insight into basic brain physiology. However, such inter-

pretations are confounded by multiple contributions to the

effect. BOLD is sensitive not only to intravascular oxy-

genation changes, but also to extravascular effects of such

changes around parenchyma and around veins draining

from activated cortex. In addition, BOLD is influenced by

alterations in voxel composition due to changes in cerebral

blood volume (CBV). Contributions of these effects to the

BOLD signal intensity changes depend on magnetic field

strength, voxel size, type of MRI experiment (spin echo/

gradient echo). Thus, there are many variables and few

observable parameters. In the previous period we have

developed a new fMRI approach that can add several es-

sential observables, namely tissue fractions, CBV and the

tissue relaxation rates. We also re-interpreted the BOLD

post-stimulus undershoot in terms of continued oxygen

metabolism and showed that, surprisingly, BOLD spin-

echo signals can occur in draining veins. The ultimate goal

of this proposal is to gain a complete quantitative under-

standing of the physiological, physical, and spatial aspects

of the BOLD effect. In AIM 1 we propose experiments to

confirm the proposed oxygen-metabolism based character

of the BOLD post-stimulus undershoot and to develop

strategies to use this undershoot for fMRI voxel selection.

e129


In AIM 2 we propose experiments that can distinguish

intravascular, extravascular, macrovascular, and microvas-

cular BOLD components. This data will be used to eval-

uate existing extravascular BOLD theories. In AIM 3 we

measure the blood transverse relaxation rates for blood in

which the transport properties of erythrocyte water chan-

nels are impaired by an aquaporin channel blocker. This

will be combined with our previous data without blocker to

evaluate the effect of exchange versus magnetic field gra-

dients on the intravascular BOLD effect. Based on our

blood data acquired in the previous grant period and our in

vivo data proposed to be acquired here, we will derive

a quantitative description for the BOLD effect that has only

physiological and physical parameters. This formalism

should allow description of the BOLD effect for all phys-

iological perturbations.


not available.

Thesaurus Terms: Brain circulation, brain imaging

/visualization /scanning, cerebrovascular imaging /visuali-

zation, functional magnetic resonance imaging, method de-

velopment, oxygen tension, oxyhemoglobin acidity

/alkalinity, blood volume, hemoglobin bioimaging /biomed-

ical imaging, clinical research, human subject




Fiscal Year: 2007


Project Start: 01-Apr-1999




IRG: RNM

TECHNIQUE DEVELOPMENT FORHYPERPOLARIZED C-13 MR STUDIES


VIGNERON, DANIEL B.

Abstract: Description (provided by applicant): This pro-

posed project is focused on developing new acquisition and

analysis techniques specifically for hyperpolarized 13C in

vivo studies. This extraordinary new technique has the po-

tential to become a major new MR metabolic imaging tech-

nique by directly observing key cellular bioenergetic

processes in vivo by MR. Hyperpolarized C imaging pro-

vides a >10,000 fold signal enhancement for detecting 13C

e130

probes of endogenous, nontoxic substances such as pyruvate

to monitor metabolic fluxes through multiple key biochemi-

cal pathways (glycolysis, citric acid cycle and fatty acid

synthesis). Recent in vivo MR studies of injected 13C labeled

substrates, pre-polarized via dynamic nuclear polarization,

have demonstrated unprecedented 13C signal enhancement

and the ability to not only observe uptake but also metabo-

lism in vivo. Our preliminary results using a DNP polarizer

developed by the GE-Amersham Malmo group have shown

the ability to acquire 3D metabolic imaging of preclinical

mouse models, for the first time, at high spatial resolution

(0.125cm3) and high SNR for not only the hyperpolarized

pyruvate, but also the metabolic products of lactate and ala-

nine in only 10 seconds. However, these studies have also

demonstrated the need for the development of specialized

MR acquisition and analysis techniques to realize the full

potential of this powerful new metabolic imaging method. To

address this need, we have assembled a multidisciplinary

research team from UCSF, Stanford University and GE

Healthcare who will work together to develop new tech-

niques for obtaining and interpreting hyperpolarized 13C MR

data. Through this project we aim to develop specialized

hyperpolarized 13C MR pulse sequences, rf detectors and

data analysis tools and evaluate them in preclinical animal

models to detect abnormal metabolism and, for the first time,

investigate metabolic changes in response to therapy with

this powerful new imaging technique. Although we have

focused the proposed technique evaluation on a transgenic

model of prostate cancer and specific drug therapies, the

techniques developed in this project would be applicable to

a variety of other animal models of disease and drug evalu-

ations. Ultimately these techniques will presumably also

benefit future clinical studies of this powerful metabolic im-

aging technique.


not available.


this project.

Institution: University Of California San Francisco

3333 California St., Ste 315

San Francisco, CA 941430962

Fiscal Year: 2008



Project End: 30-Apr-2011



IRG: BMIT


IN VIVO DETECTION OF TRABECULARBONE STRUCTURAL ANISOTROPY USINGPARALLEL MRI

Grant Number: 1F31EB007448-01A1

Wald, Michael

Abstract: Description (provided by applicant): Metabolic

bone disease, particularly osteoporosis, is a serious chal-

lenge to our health system. In the United States, treatment

costs for osteoporosis is currently estimated at $10-$18

billion and expected to double over the next decade as the

population ages. Currently, fracture risk is diagnosed by

bone density measurements. Substantial improvement in

the determination of fracture risk can be gained through

knowledge of both bone density and trabecular bone (TB)

structural integrity. The fabric tensor provides both a mea-

sure of bone density (scalar) and the structural orientation

of TB (2nd-rank tensor). Magnetic resonance imaging

provides a non-invasive means of examining both bone

density and trabecular bone microstructure. Yet, technical

limitations of in vivo MRI, the achievable signal-to-noise

(SNR) and field-of view (FOV) within a reasonable scan

time prevent an accurate determination of the fabric tensor.

We propose that the TB fabric tensor and its structural

anisotropy can be quantified in vivo, thereby improving

the diagnostic sensitivity to disease progression and treat-

ment efficacy. Our long-term specific aims include (i)

implementation of parallel imaging at higher field

strengths for the acquisition of a larger TB volume for

improved analysis of the fabric tensor without SNR deg-

radation, (ii) development of novel image processing

techniques robust to noise and partial-voluming for the

characterization of TB structure, and (iii) validation of the

fabric tensor through comparison to finite-element calcu-

lations of theTB stiffness tensor from high resolution

datasets.


not available.


this project.


3451 Walnut Street


Fiscal Year: 2007


Project Start: 01-Dec-2007

Project End: 30-Nov-2009



IRG: ZRG1

CLINICAL SUMMER IMMERSION FORBIOMEDICAL ENGINEERING PHDSTUDENTS


Wang, Yi

Abstract: Description (provided by applicant): The objec-

tive of this proposed clinical summer immersion program is

to provide substantial clinical experiences for biomedical

engineering graduate students to help shape their under-

standing and appreciation of challenges in medicine. This

program will be offered to the first year Biomedical Engi-

neering PhD students. During their first summer break, the

students will be placed at the Weill Medical College of

Cornell University campus for 10 weeks of full time im-

mersion in clinical practice. Each student will be assigned to

a clinician mentor. The students will shadow the practice of

clinician mentors and their partners, engage in focused study

of specific organ anatomy, diseases, and diseases’ diagnoses

and treatments, participate in ongoing research directly re-

lated to clinical practice, and attend lectures on bioethics and

ongoing clinical seminars. Additionally at the Ithaca

Engineering campus of Cornell University, the students will

register for and attend introductory lectures in the preceding

spring semester necessary for matching students and clinician

mentors and participate in a concluding seminar at the Bio-

medical Engineering Department the following fall semester.

The specific aims for the clinical summer immersion program

are: 1) To introduce students to the principles underlying

medical ethics and the responsible conduct of research. 2) To

provide the students a basic understanding of the diagnostic

and therapeutic procedures and technologies in a specific

clinical practice area, such as Radiology, Cardiology, Sur-

gery, Pediatrics, Urology or Orthopedics. 3) To guide stu-

dents through a focused independent clinical study with

a clinician mentor.


not available.


this project.

Institution: Weill Medical

College Of Cornell Univ

1300 York Avenue

New York, NY 10021

e131


Fiscal Year: 2008






IRG: ZEB1

TRAINING IN QUANTITATIVE MAGNETICRESONANCE IMAGING


Wehrli, Felix W.

Abstract: Description (provided by applicant): Magnetic

resonance imaging (MRI) has, since its inception three de-

cades ago, been by far the most complex but also the most

versatile imaging technique since the possibilities by which

the spin system can be manipulated are almost limitless. The

technique’s complexity and extraordinary richness therefore

require rigorous training. Although inherently quantitative,

MRI has been used largely as a qualitative imaging technique

practiced by radiologists utilizing predominantly qualitative

criteria for establishing a diagnosis or excluding disease. This

approach is fraught with problems, its main disadvantage

being the subjective nature of the result, i.e. sensitivity to

reader experience and judgment. Many problems in diag-

nostic medicine require a quantitative assessment. Moreover,

for many diagnostic or staging problems quantitation of an

observation is not merely a better option but the qualitative

approach is entirely unsuited. Examples are measurement of

tissue perfusion, quantification of metabolite concentration

by spectroscopic imaging or the assessment of non-focal

systemic disorders such as Alzheimer’s disease or metabolic

bone disease where a quantitative measurement of some

structural or functional parameter has to be made. In diag-

nostic imaging in general, and MRI in particular, quantitative

approaches require the tools of post-processing of arrays of

images, typically performed off-line on workstations. This

process is multidisciplinary, requiring close cooperation

among physicians, MR physicists, and computer scientists,

which is not possible without effective cross-training.

Physicists, engineers and computer scientists usually lack an

understanding of the medical problem and are often unable to

translate abstract concepts to the physician. This training

program, for which continued support is sought, aims to train

three predoctoral and three postdoctoral basic science

trainees per year in quantitative MRI methodology focusing

on MR image acquisition, reconstruction and postprocessing

e132

tools for diagnosis and treatment monitoring. Training mo-

dalities involve a combination of colloquia, structured

teaching and hands-on laboratory training, with particular

emphasis on preceptor-directed research. The training faculty

consists of both basic scientists and physicians who have

a record of successful multidisciplinary research training.


not available.


this project.


3451 Walnut Street


Fiscal Year: 2008






IRG: ZEB1

QUANTITATIVE MAPPING OF THEINTERVERTEBRAL DISC

Grant Number: 5F31EB006299-02

Witschey, Walter Rt.

Abstract: Description (provided by applicant): Degenerative

disk disease (DDD) is a serious musculoskeletal disorder

challenging our health system and includes a number of

clinical diagnoses such as mechanical cervical and lumbar

pain, degenerative scoliosis and spinal stenosis. A novel MRI

pulse sequence design for quantitative tissue diagnosis using

magic echo relaxation mapping has emerged - this technique

may be superior to current T2 relaxation mapping. This

strategy is particularly sensitive to water molecules bound

and intermediately bound toglycosaminoglycans in the nu-

cleus pulposus and may serve as an early-stage reporter of

structural changes associated with DDD. We suspect that

magic echo relaxation mapping correlates with the macro-

molecular content of the intervertebral disc and can detect

biochemical and biomechanical changes that precede DDD

morphological changes. Our long-term specific aims include

(i) a measurement of the precision and spatial distribution of

magic echo relaxation times in both healthy and proteoglycan-

depleted bovine and human cadaveric specimans, (ii) a test for

correlation between magic echo relaxation times and changes

observed in tissue biochemistry andbiomechanics. We also

propose to quantify the proton-proton dipolar coupling


constant among compartments of the intervertebral disc. Rel-

evance to public health lower back pain is a significant medical

and economical burden in the United States. For among 90%

of individuals with lower back pain, however, the source of the

pain cannot be identified and a specific diagnosis is not pos-

sible. We employ quantitative magic echo relaxation mapping

to observe the biochemical and structural changes that occur

during degenerative disc disease in the hope that we may

quantify these changes earlier and with even greater sensitivity

than the current discographic techniques.


not available.


this project.


3451 Walnut Street


Fiscal Year: 2008






IRG: ZRG1

DEVELOPMENT OF ARTERIAL SPINLABELING FOR CLINICAL APPLICATIONS


Wong, Eric C.

Abstract: Description (provided by applicant): Stroke is

a devastating disease that is caused by a lack of perfusion

to the brain, and is the third leading cause of death in the

US. Arterial spin labeling (ASL) is an MRI based method

for noninvasive imaging of perfusion, using no radiation

and no injections, and holds tremendous potential for aid-

ing in the diagnosis and management of stroke. The overall

objective of this project is to develop two new ASL

methods for the evaluation of cerebrovascular diseases,

with stroke as the primary focus. The first is Velocity Se-

lective ASL (VSASL), which addresses the inability of

conventional ASL techniques to measure cerebral perfusion

in the presence of collateral and/or slow flow, a condition

that is often present in stroke patients. In conventional

ASL, radiofrequency pulses magnetically tag arterial blood

in major arteries leading to the brain. Under conditions of

slow or collateral flow, the tag, which decays away with

a half life of approximately one second, can dissipate

before it can be delivered to the target tissue, and can give

a false reading of no perfusion. In VSASL, arterial blood is

tagged based purely on flow velocity, rather than location,

allowing for tagging in all locations simultaneously.

VSASL is currently the only ASL technique that can in

principle give accurate measures of perfusion under these

conditions. Our specific aims related to bringing VSASL

into clinical practice are: 1) Development of a robust 3D

image acquisition method for VSASL; 2) Development of

a direction independent VSASL tagging method; and 3)

Optimization of VSASL for the detection of slow flow. The

result of this work will be a robust ASL method for

quantitative perfusion imaging in stroke. The second

method is Vascular Source Imaging (VSI), which allows

for the identification of the vascular source that supplies

blood to the tissue of interest. VSI is a new technique with

a broad range of potential clinical applications including

the evaluation of carotid stenosis, risk assessment for

stroke, and the identification of tumor blood supplies. VSI

is early in it’s development, and our aims in this area are to

address two basic technical issues: 1) Optimize VSI tag-

ging parameters based on pseudo-continuous labeling; and

2) Develop efficient VSI encoding schemes to maximize

the SNR of the VSI measurement and allow for

simultaneous encoding of multiple arteries. The result of

this work will be robust methods for measuring not only

the amount of perfusion, but also the vascular source from

which that perfusion was derived.


not available.

Thesaurus Terms: Blood, perfusion, stroke artery, base,

birth, brain, catalog, conditioning, death, density, diagnosis,

hospital equipment /supply, lead, magnetic resonance imag-

ing, measurement, motivation, neoplasm /cancer blood sup-

ply, noise, pathology, radiation, reading, tag term, tissue

clinical research

Institution: University Of California

San Diego

9500 Gilman Dr, Dept 0934

La Jolla, CA 920930934

Fiscal Year: 2008






IRG: BMIT

e133


FUNCTIONAL MRI IN HUMANS AT 7 TESLA


Yacoub, Essa

Abstract: Description (provided by applicant): Currently, the

vast majority of magnetic resonance imaging and functional

imaging studies are conducted at relatively low magnetic fields

of 1.5 or 3.0 Tesla. However, theoretical considerations as well

as experimental evidence have suggested that there is a funda-

mental dependence of image signal to noise ratios, functional

imaging contrast and spatial specificity on the magnetic field

strength. More recently, it has been suggested that even routine

anatomic imaging has potential advantages at high magnetic

fields. Thus far, in humans, functional imaging studies have

only been done at fields as high as 7 Tesla. Much of the ex-

perimental data suggesting advantages for higher field studies

have been acquired using animal models. While animal studies

provide us with data that can elucidate the biophysics of MRI/

fMRI in certain cases, they are not necessarily fully applicable

to the human brain. Furthermore, almost all of the studies in

humans or animals at high magnetic fields have been done

using limited field of views and / or a single or few slices.

Shorter T2*s, increased susceptibility effects, increased phys-

iological noise, increased SAR, and inhomogeneous B1 fields

can all hinder the advantages offered by high magnetic fields.

To alleviate some of the problems associated with these issues

and thereby making high field imaging more attractive for

general applications of the whole brain, technical development

is required. With the recent growth and development of parallel

imaging and parallel imaging techniques, including transmit

and receive coil arrays, many of these problems commonly

observed at high magnetic fields can be addressed. In addition,

sequence modification and new sequence design can also help

to significantly reduce the technical problems associated with

high field studies. The general aim of this proposal is devel-

opment of fMRI and MRI techniques for whole brain acquisi-

tions at high magnetic fields (7 T & 9.4 T). In achieving this

aim, fMRI/MRI studies will be conducted at the ultra-high

magnetic field of 9.4 Tesla for the first time in humans. Fur-

thermore, we will systematically compare the advantages of

higher field systems with lower field systems (3 T) for general

applications.


not available.

Thesaurus Terms: Evaluation /testing, functional magnetic

resonance imaging, technology /technique development

brain mapping, magnetic field, neurophysiology bioimaging

/biomedical imaging, clinical research, human subject

e134

Institution: University Of Minnesota Twin Cities

450 Mcnamara Alumni Center

Minneapolis, MN 554552070

Fiscal Year: 2008


Project Start: 01-Jul-2002




IRG: BMIT

MRI EVALUATION OF TUMOR GROWTHAND TREATMENT RESPONSE

Grant Number: 5K25EB005936-04

Yankeelov, Thomas E.

Abstract: Description (provided by applicant): The research

proposed aims to develop and apply new methods for the

quantitative evaluation of tumor growth and treatment response

by magnetic resonance imaging (MRI) at the theoretical, pre-

clinical, and clinical levels. In particular, we propose to develop

and implement novel approaches to quantitative tissue char-

acterization using dynamic contrast enhanced MRI (DCE-

MRI), and to integrate these measurements with quantitative

metrics derived from other imaging modalities and MR

methods. These methods can non-invasively acquire informa-

tion on, for example, a tumor’s cell density, necrotic fraction,

neovascularization, and vascular endothelial integrity – all of

which have been shown to be promising reporters on tumor

growth and treatment response. Thus, a major goal is to develop

noninvasive imaging biomarkers that can serve as surrogates

for disease response. We will incorporate other existing and

emerging imaging methods into the proposed DCE-MRI

studies; namely, diffusion weighted MRI (DW-MRI), FDG-

PET, CT, and optical methods, and compare their relative

performance separately and in combination. DW-MRl mea-

surements report on a tissue’s cellularity and have been shown

to correlate with favorable treatment response; FDG-PET re-

ports on tissue metabolism and therefore provides information

on cell proliferation rates; CT provides high resolution struc-

tural information which will facilitate co-registration of the MR

and PET indices; and optical imaging will be employed to lo-

cate metastases in a mouse tumor model. Combing the func-

tional information provided by DCE-MR1 techniques, the

structural information provided by DW-MRI and CT, and the

metabolic information of FDG-PET provides a formidable

means of assessing of tumor growth and treatment response. To

the best of our knowledge, such quantitative multi-parametric


studies of tumors have not yet been performed. Moreover, these

studies will make use of high field (3 T for humans; 9.4 T for

animals) MRI which offer higher signal-to-noise ratio mea-

surements not previously obtainable. To realize the goal of

developing quantitative, accurate, reproducible, and easily

implemented methods to characterize tumor growth and treat-

ment response, we have identified three basic Specific AimsI)

development of appropriate mathematical models to evaluate

DCE-MRI data accurately and quantitatively; II) apply and

validate these methods in the MMTV-PyVT transgenic mouse

model of human breast cancer; III) apply a subset of these

methods to evaluate human breast cancer treatment response.


not available.

Thesaurus Terms: Breast neoplasm, image processing,

magnetic resonance imaging, mathematical model, neoplas-

tic growth breast neoplasm /cancer diagnosis, diagnosis de-

sign /evaluation, noninvasive diagnosis bioimaging

/biomedical imaging, clinical research, computed axial to-

mography, diffusion magnetic resonance imaging, female,

genetically modified animal, human subject, laboratory

mouse, patient oriented research, positron emission tomog-

raphy

Institution: Vanderbilt University

Medical Center

Nashville, TN 372036869

Fiscal Year: 2008






IRG: NCI

ACCESSIBILITY ENHANCEMENTS FORITK-SNAP 3D MEDICAL IMAGESEGMENTATION SOFTWARE


Yushkevich, Paul A.

Abstract: Description (provided by applicant): Segmenta-

tion of brain structures and lesions is a recurrent problem in

neuroscience. Software tools that combine advanced

mathematical methodology with well-designed easy-to-use

human interfaces can help neurologists produce more ac-

curate segmentations in less time. ITK-SNAP is a multiplat-

form open source application that provides an intuitive

interface for user-guided segmentation of 3D images using

the active contour approach, along with a set of supporting

interfaces for manual structure delineation and 3D image

navigation. ITK-SNAP has been demonstrated to improve

segmentation reliability and efficiency over manual delinea-

tion and it is already helping many researchers meet their

segmentation needs. ITK-SNAP is available freely through

its own Internet site, which supports a growing user com-

munity. The objective of this proposal is to make ITK-SNAP

accessible to a much wider audience of neuroscientists by

making improvements to its interoperability, usability and

documentation. Interoperability enhancements include

comprehensive support for the NIFTI and DICOM image

formats, with a special emphasis on correct interpretation of

the transformations between image space and patient space

encoded in NIFTI and DICOM headers. Proposed usability

enhancements include the ability to load and process multiple

image layers at once, enabling concurrent segmentation of

multi-modality imaging data, segmentation of white matter

structures in diffusion-weighted MRI, and other segmen-

tation applications for which limited software resources exist

today. New documentation will describe several scenarios

that combine ITK-SNAP with prominent neuroimaging tools

like SPM and AFNI to create task-oriented image analysis

pipelines that leverage segmentation. In addition to making

ITK-SNAP more accessible, this proposal aims to integrate it

with the NIH Neuroimaging Informatics Tools and Re-

sources Clearinghouse (NITRC). This effort will help expose

many more users to the tool and create an environment in

which users and developers can interact productively, leading

to additional high-impact enhancements to interoperability

and usability. This application proposes to improve the in-

teroperability, usability and documentation of ITK-SNAP,

a software application that helps neuroanatomists delineate

brain structures and lesions in three-dimensional medical

images more quickly and more accurately. The proposed

effort will make the tool more accessible and available to

more biomedical researchers and, subsequently, will have an

impact on the cost-efficiency and accuracy of various clinical

studies and intervention procedures.


not available.


this project.


3451 Walnut Street


Fiscal Year: 2007


e135






IRG: ZNS1

RF COILS FOR PARALLEL MRI/MRS INVIVO AT HIGH FIELDS


Zhang, Xiaoliang

Abstract: Description (provided by applicant): High and ultra-

high field (3-9.4 Tesla) magnetic resonance imaging and

spectroscopy (MRI/MRS) has been proven to be fundamen-

tally advantageous due to their intrinsically high sensitivity.

Recently, with the advent of new reconstruction algorithms

such as SENSE and SMASH, parallel imaging, a fast imaging

technique introduced some 20 years ago has been revived and

has become practical and robust. This technique can dramati-

cally reduce the minimum data acquisition time without sacri-

ficing sensitivity. A technique combining parallel imaging with

high-field MR is desired and will be ideal because it possesses

both the advantages of fast acquisition time and high sensitiv-

ity. However, due to high operating frequencies at high fields,

both parallel imaging and high-field MR confront RF coil de-

sign challenges such as increased radiation losses, difficult to

achieve coil decoupling, increased coil/subject interactions,

and complicated design and operation. These challenges have

become a major obstacle for further development of parallel

imaging at high fields. Therefore, we propose a comprehensive

project in this application based on our newly developed mi-

crostrip transmission line (MTL) coil design concept. The

major goals will be focused on (i) development of a wide va-

riety of efficient high-frequency RF coil arrays for in-vivo high-

field parallel imaging using the MTL concept; and (ii) the es-

tablishment of a simulation, modeling a wide variety of parallel

MTL coil arrays for the analysis of resonant frequencies, de-

coupling and B1 and E fields, numerically. The proposed coil

arrays are characterized by unmatched advantages of (i)

a completely distributed circuit design, (ii) a high Q factor and

better sensitivity, (iii) unique and efficient decoupling mecha-

nisms, and (iv) simple and compact coil design, with easy

fabrication and low cost. Successful outcomes from this re-

search will provide a robust solution to RF coil array designs for

parallel imaging at high fields and result in significant techno-

logical advances in high-field RF coil array engineering. They

will be important to the future success of in vivo high-field

parallel MRI/MRS.

e136


not available.


image enhancement, magnetic resonance imaging, nuclear

magnetic resonance spectroscopy magnetic field, radiowave

radiation bioimaging /biomedical imaging, clinical research,

human subject

Institution: University Of California

San Francisco

3333 California St., Ste 315

San Francisco, CA 941430962

Fiscal Year: 2008






IRG: BMIT

FLAT-PANEL X-RAY IMAGING DETECTORWITH AVALANCHE GAIN


Zhao, Wei

Abstract: Description (provided by applicant): The objec-

tives of this proposal are to demonstrate the feasibility of an

indirect flat-panel detector with programmable gain based on

structured scintillator - cesium iodide (Csl), avalanche

amorphous selenium (a-Se) photoconductor (which we call

HARP) with increased gain and active matrix (AM) thin film

transistor (TFT) readout, and improve the low dose imaging

performance of flat-panel x-ray imaging detectors. We call

the detector under investigation SHARP-AMFPI (Scintillator

HARP Active Matrix Flat Panel Imager). It will provide

better image quality in fluoroscopy, behind dense breasts in

mammography, and digital tomosynthesis, where existing

flat-panel detectors fall short of quantum noise limitation.

Furthermore the inherent high electric field and charge carrier

mobility in HARP allows better temporal imaging perfor-

mance which leads to less image artifacts and better diagnosis

accuracy. The specific aims are to: (1) understand and opti-

mize the fundamental imaging properties of Csl and HARP

for different x-ray imaging applications; (2) demonstrate the

excellent low dose and high speed performance of SHARP

using a prototype HARP tube optically coupled to optimized

Csl layers; (3) identity potential practical difficulties for

constructing SHARP-AMFPI and develop engineering

methods for solving them; (4) demonstrate the practical


feasibility of the proposed detector. Our research design and

methods are to develop experimental and modeling tech-

niques to investigate the fundamental imaging properties of

Csl and HARP, verify the validity of models with experi-

mental results so that the model can be used to optimize de-

tector design parameters. We will investigate the feasibility

of the detector using three gradual steps: First, the advantage

of avalanche gain on image quality will be demonstrated

using the matured electron beam readout technology for

HARP, then a hybrid prototype detector will be made based

on existing TFT array and HARP layer deposition technol-

ogy so that compatibility issues between these two devices

can be fully investigated, and finally a integrated prototype

detector will be constructed using procedure that is scalable

to large areas to demonstrate the ultimate feasibility of

SHARP-AMFPI. Its x-ray imaging performance will be

evaluated and compared to existing FPI technologies, so that

its improved performance at low dose and high frame rates

can be demonstrated.


not available.


image enhancement, radiation detector, radiography bioen-

gineering /biomedical engineering, fluoroscopy, mammog-

raphy, mathematical model, model design /development,

photoconduction, scintillation camera, tomography bioi-

maging /biomedical imaging, electrical measurement

Institution: State University New York

Stony Brook

Stony Brook, NY 11794

Fiscal Year: 2007






IRG: ZRG1

AIDED DETECTION OF PULMONARYEMBOLISM ON CT PULMONARYANGIOGRAPHY


Zhou, Chuan

Abstract: Description (provided by applicant): Pulmonary

embolism (PE) is a leading cause of death in the United States

if untreated. Prompt diagnosis and treatment can dramatically

reduce the mortality rate and morbidity of the disease.

Computed tomographic pulmonary angiography (CTPA) has

been reported to be an effective means for clinical diagnosis

of PE. Interpretation of a CT scan for PE demands extensive

reading efforts from a radiologist who has to visually track

a large number of vessels in the lungs to detect suspected PEs.

Despite the efforts, the sensitivities were reported to range

from 53% to 100%. Preliminary results from the PIOPED II

study indicated a sensitivity of 83% by multi-detector CTPA.

Computer-aided diagnosis (CAD) can be a viable approach to

improving the sensitivity and efficiency of PE detection in

CTPA images, as well as reducing inter-observer variability.

The overall goal of the proposed project is to develop a robust

CAD system that can provide a systematic screening of PE on

CTPA scans and serve as a second opinion by automatically

alerting the radiologists to suspicious locations on 2D slice

and 3D volume rendering display of the CTPA images. We

will develop advanced computer vision techniques to en-

hance the characteristics of vessels, automatically extract the

pulmonary vessels, reconstruct the vessel tree, detect candi-

date PEs, differentiate PE from normal pulmonary structures,

and identify the true PEs. The techniques will be specifically

designed for analysis of the complex vascular structures on

CTPA images. The specific aims of this project include: (1)

developing image preprocessing method to enhance vessel

characteristics, (2) developing a new rolling balloon tech-

nique in combination with structure analysis to track vessels

accurately, including vessels partially or completely oc-

cluded by PEs, (3) developing multi-prescreening method for

the identification of suspicious PEs at different levels of ar-

tery branches, especially for PEs in small subsegmental ar-

teries, (4) analyzing PE features for development of

classification methods, (5) developing false positive reduc-

tion method based on feature analysis and fuzzy rule-based,

linear, or neural network classifiers, (6) exploring perfor-

mance evaluation methodology for computerized detection

of PEs, and (7) performing observer ROC study to evaluate

the effects of CAD on radiologists’ accuracy in PE diagnosis.

The relevance of this research to public health lies in the fact

that there is substantial false-negative diagnosis of PEs. CAD

will potentially reduce missed PEs and improve the chance of

timely treatment of patients, thus reducing the mortality rate

and speed up recovery from this condition.


not available.

Thesaurus Terms: Angiography, computer, diagnosis,

health science profession, pulmonary circulation obstruction,

radiology archive, artery, base, classification, conditioning,

death, gold, information system, lead, lung, performance,

e137


public health, reading, reduction, social behavior disorder,

training, vision clinical research

Institution: University Of Michigan At Ann Arbor

3003 South State Street, Room 1040

Ann Arbor, MI 481091274

Fiscal Year: 2007

e138


Project Start: 01-Mar-2006

Project End: 28-Feb-2009



IRG: BMIT

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