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Shreis Health Inc. Proprietary & Confidential Rotational Field Quantum Magnetic Resonance in Tissue...

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Shreis Health Inc. Propr Rotational Field Quantum Rotational Field Quantum Magnetic Resonance in Tissue Magnetic Resonance in Tissue Engineering Engineering A Preliminary Experience A Preliminary Experience Dr. R. V. Kumar Center for Advanced Research and Development & Institute of Aerospace Medicine, Indian Air Force, Bangalore
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Shreis Health Inc. Proprietary & Confidential

Rotational Field Quantum Magnetic Rotational Field Quantum Magnetic Resonance in Tissue EngineeringResonance in Tissue Engineering

A Preliminary ExperienceA Preliminary Experience

Dr. R. V. Kumar

Center for Advanced Research and Development

&

Institute of Aerospace Medicine,

Indian Air Force, Bangalore

Rotational Field Quantum Rotational Field Quantum Magnetic ResonanceMagnetic Resonance

Establishing Communication with

Living Cells

Centre for Advanced Research and Development (CARD)

Institute of Aerospace Medicine (IAM) Bangalore

Where did it all start..Where did it all start.. In 1996, the Centre for Advanced Research and

Development (CARD), initiated a project to study the effect of modulated Radio Frequency (RF) in the so far unexplored frequency band of 1 kHz to 10 MHz.

Our engineers by simulation established that, when a biological Cell is exposed to such RF under a instantaneous magnetic field of several Tesla should alter many cell parameters, including its resting Transmembrane Potentials (TMP)

Where did it all start..Where did it all start.. Many Cellular activity is closely linked with

the TMP. TMP plays an Important role in the synthesis of many proteins (Cone CD. et. al., Variation of transmembrane potential level as a basic mechanism of mitosis control : Oncology: 1970;24:438-470)

Powerful Mathematical Models and real time simulation in combination with MRI data of the tissue is used to precisely alter transmembrane potentials of target tissue.

The Hypothesis..The Hypothesis.. Selectively altering TMP, can initiate synthesis of HSP

group of proteins or P53 group of proteins that generally control mitotic activities in biological systems.

Alternatively, Rotational Field Quantum Nuclear Magnetic Resonance (RFQMR) is probably triggering the msx1, BMP4, and the NOTCH group of Genes that is dormant in mammals, but is well expressed in primitive biological systems, where dedifferentiation of terminally differentiated cells and redifferentiation in to specific organs cells is well established eg. In Salamander or Zebra fish. (Shannon J Odelberg., et.,al,. Dedifferentiation of Mammalian Myotubes Induced by msx1; Cell: 103; 1099-1109; Dec. 22, 2000).

In Cancer....In Cancer....We need to understand Cytonics, the electronics of

the biological cell, it’s control and communication. We have, to a large extent understood the Phenome and the Genome but very little on cellular cytonics.

CARD has in the past few years, accrued considerable data to work on Cytonics of neoplastic cells. A lot remains to be proved, but it is a good and humble beginning.

The Technology…..The Technology….. The RFQMR or the Cytotron Technology was patented

by us under PCT. The Cytotron Device will deliver precise dose of RF

radiation in the unexplored 1Khz to 10 MHz Range in the presence of high instantaneous magnetic field, which is perfectly focused. There has been anecdotal reference of MRI, providing significant changes in patients with depression not responding to other treatments.

Cytotron has been in use for the last two years for the treatment of Osteoarthrites and Cancer as part of a clinical trial.

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A small bit of the theory...A small bit of the theory... Problem of RF wave incidence on a lossy medium (tissue) Incident RF energy is reflected and refracted at the interface of air and

tissue Fundamental constants defining how much is reflected and refracted

are parameters of the medium

Biological TissueAir

Ei

SiHi

Et

StHt

Er

Sr Hr

Inte

rfac

e

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RFQMR incidenceRFQMR incidence Relative amplitudes of the reflected and transmitted

components of the incident electric field wave are defined below:

Reflection coefficient, gamma, and, appropriately, transmission coefficient, tau, are determined purely by the parameters of the two media of conduction:

E r E i (1a)

E t E i (1b)

1 2

1 2

(2a)

2 1

1 2

(2b)

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Parameters of mediaParameters of media Permittivity, , defines the polarizability of a material

– Applied E-field gives rise to dipole moment distribution in atoms or molecules

– Secondary fields are set up, thus net E-field is different– If dipole moment distribution is denoted by vector P, the relationship

between applied electric field and P is:

Conductivity, , summarizes the microscopic behavior of conductors– Applied E-field gives rise to electron drift– This drift results in a current density in the direction of the E-field– Conductivity is the factor which relates the E-field to the drift

current

P ( 0)

E (3)

J

E (4)

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Parameters of mediaParameters of media Permeability, , is analogous to the permittivity in that it describes the

relationship between the magnetic dipole vector and the magnetic field

– Most of the cells and tissues that will be of interest are non-magnetic

– For these types of materials, is considered to be equivalent to 0, the permeability of free space

– It is, therefore, much less critical to our analysis of RF interaction with biological tissue than permittivity and conductivity

These three parameters fundamentally characterize any medium macroscopically

– Parameters can be used to determine depth of penetration and absorbed power of an incident RF wave on the medium

B

H (5)

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Permittivity of tissuesPermittivity of tissues

101 102 103 104 105 106 107 108 109 1010 10110

1

2

3

4

5

6

7

8

Frequency (Hz)

log

Relat

ive P

erm

ittivi

ty

Relative Permittivity versus Frequency for Six TissuesDry SkinWet SkinMuscleBloodBrain, White MatterFatPronounced Drop in Permittivity

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Conductivity of tissuesConductivity of tissues

101 102 103 104 105 106 107 108 109 1010 1011-4

-3

-2

-1

0

1

2

Frequency (Hz)

log

Cond

uctiv

ity (S

/ m

) Conductivity versus Frequency for Six Tissues

Dry SkinWet SkinMuscleBloodBrain, White MatterFat

Significant Increases in Conductivity

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Depth of penetrationDepth of penetration Any wave that enters a lossy medium will be attenuated

after some distance Depth of penetration (D.O.P.) characterizes the distance

after which the field intensity is 1 / e of its incident value For a low-loss dielectric medium, the D.O.P. is described

by the following equation, in which tan(c) is the loss tangent of the material

D.O.P.c 2

rr '[ 1 tan2c 1]1/ 2(6)

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DOP of tissuesDOP of tissues

101 102 103 104 105 106 107 108 109 1010 1011-4

-3

-2

-1

0

1

2

3

4

5

Frequency (Hz)

log

Dep

th o

f Pen

etratio

n (m

eters)

DOP versus Frequency for Six TissuesDry SkinWet SkinMuscleBloodBrain, White MatterFat

Shreis Health Inc. Proprietary & Confidential

Non-ionizing radiationNon-ionizing radiation Microscopic effects of non-ionizing RF energy have been studied

extensively over the past few decades because we are exposed to these waves more often than ever before

However, many mechanisms of interaction are still not well known nor are relevant results consistent

In contrast, effects and health/safety standards are widely accepted in the science community

Level of understanding of mechanisms of interaction decreases as we move from extracellular (membrane) to intracellular (enzyme, DNA) components

We will consider these effects of non-ionizing radiation in two separate frequency bands, distinguished by the relative size of wavelength versus medium (human body)– Low Radio frequency radiation: >> D– MHz Radio frequency radiation: ~ D, << D

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VL

F

LF

30kH

z

300k

Hz

Lower frequenciesLower frequencies

Power Lines

Submarine Comm.

Audio (sound)

Radio beacons (Navigation)

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Low frequency RF effectsLow frequency RF effects Prevailing theory is that interactions occur primarily in the plasma

membrane, then a cascade of changes propagates from the membrane to the nucleus of the cell as shown below2:

An alternate theory suggests the possibility that low frequency RF interacts directly with the nucleus and the DNA based on the following analysis– Membrane blocks low-level electric fields but not magnetic fields– Although cellular dimensions limit the induced electric field resulting

from the penetrating magnetic field to very small values, the magnetic field itself may interact with cellular components

– Recent studies by Blank and Goodman show that the magnetic field may interact with enzymes and DNA within the cell through classical physics based mechanisms

PlasmaMembrane

CellularMembrane

Enzymes,Genes,

Proteins

BiochemicalMessenger Nucleus

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Theory of signal transductionTheory of signal transduction First, consider the signal transduction theory in which an enzymatic cascade is

responsible for changes in biosynthesis

The following is a step by step account (from Behari 1999) of how the signal reaches the DNA in order for changes in biosynthesis to occur: – Faraday induction creates currents in the ionic aqueous solution of the

plasma membrane– These currents are blocked by the strong dielectric barrier of the cell

membrane; however, they cause changes in the cell surface involving counter ion layer, ion channel permeability, glycoproteins, and ligand receptors

– Consequently, there is enzyme activation, gene induction, protein synthesis, and mitogenesis / cell proliferation / retardation

– Secondary biochemical messengers then pass this signal to the nucleus and the DNA of the cell

PlasmaMembrane

CellularMembrane

Enzymes,Genes,

Proteins

BiochemicalMessenger

Nucleus,DNA

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Direct interaction theoryDirect interaction theory Many current studies present possible direct RF interaction

mechanisms with DNA to explain changes in biosynthesis of the cell exposed to Controlled RF under the influence of high magnetic fields– Blank suggests Mobile Charge Interaction (MCI) model from a

variety of experiments. Magnetic fields interact with moving charges via the classical

electromagnetic relation:

In the case of intracellular flowing charges, such as enzymes, this force will result in a change in velocity and a resulting alteration in intended biological function (demonstrated in Na, K-ATPase and cytochrome oxidase reactions)

In addition, moving electrons in DNA helices will begin to experience forces which may repel them from each other and bend, or even break, the chain, resulting in increased DNA multiplication

BvqF

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DNA chain bendingDNA chain bending

A direct result of equation (7) is the relationship between flowing charge (current), magnetic field, and induced force shown in equation below

When two wires have currents flowing in opposite directions, an applied magnetic field will cause repulsion

Expanding this idea by thinking about the DNA helix simply as two “wires” which may carry charge through electron transport in opposing directions, we expect chain bending in some instances:

F I dl

B (8)

II

B

F

FAftertime I I

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MHz Radio frequenciesMHz Radio frequencies

RF

300k

Hz

300G

Hz

AM Broadcasting

TV Broadcasting, FM Radio

Cellular Phone

Microwave Oven

Satellite Comm.

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Where does RFQMR fit on the EM Where does RFQMR fit on the EM SpectrumSpectrum

Sub-Radio and Near-Radio, A part of the spectrum used for the first time in Medical Field. Currently used in Oceanography and

Submarines

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MHz Radio frequency effectsMHz Radio frequency effects Mechanisms of interaction for RF radiation on the body are very

different at low-levels of radiation versus higher levels Low-level RF radiation causes predominantly non-thermal effects

because the intensity is not high enough to significantly change tissue temperature– Non-thermal effects are direct interactions of RF with biological cells– Very important because most common exposure is at low-levels – Not as well understood: specifically, mechanisms are not fully explored

nor consistently documented High-level RF radiation causes thermal effects

– Thermal effects are indirect interactions: EMF -> heat -> biological effect– RF energy and, specifically, Specific Absorption Rate (SAR), are high

enough to significantly heat the tissue– Hazards are well established, safety levels are well documented

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Non-thermal effects of MHz RFNon-thermal effects of MHz RF RF fields induce torque on molecular dipoles which can result in ion

displacement, vibrations in bound charges, and precession This effect is characterized by the Bloch Equation which is

fundamental to MR Imaging

With an applied magnetic field, the nuclear spins will precess in a left-hand direction around the field with angular frequency proportional to its amplitude

No observable biological hazards have been noted as a result of these mechanisms because they are outweighed by random thermal agitation in low-level fields

d

M

dt

M

B (9)

THE CYTOTRON THE CYTOTRON

THE CYTOTRON THE CYTOTRON

Typical RFQMR Gun AssemblyTypical RFQMR Gun Assembly

RFQMR can be successful in …….RFQMR can be successful in ……. the non-invasive treatment of…….

Many Degenerative Diseases like, Osteoarthrites, Osteoporosis, Tendenitis, aseptic necrosis, Migraine, acute burns, drug resistant epilepsy, diabetic neuropathy, peripheral and coronary Angiogenesis grow new blood vessels in the heart muscle in place of a bypass surgery

etc.,

where ever Tissue Regeneration is essential…...

With RFQMR…...With RFQMR…... We will be able to communicate with the cancer cells

in cancer patients and take over the cell’s command and control and effect successful degeneration by,

1. Directly halting active cell division.

2. Opening up Protein path ways to allow Chemotherapy molecules without effecting other healthy cells.

3. Or guide glucose coated ferrite nanoparticles into the tumor cells and Rip them apart.

Regenerative and Degenerative Experiences with RFQMR

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OSTEOARTHRITISOSTEOARTHRITIS

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OSTEOARTHRITISOSTEOARTHRITIS

PainRestriction of movementsOption - surgery

Inclusion: Volunteers posted for Knee Replacement Surgery.

Presentation:

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RESULTSRESULTS

International Knee society rating system

-Range of knee movement-Pain score-Dynamometry-Total knee score-Functional knee score

Radiological Evidence Quality of Life (FACT)

Evaluation Criteria

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PREPOST

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PRE POST

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CANCER

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CMP in Living Cell …...CMP in Living Cell …...Altering the Cell Membrane Potential (CMP) is a complex process. However….

-70 to -90 mV is the CMP in Healthy Cells. -40 to -60 mV when Infected. -20 to -30 mV in Cancer and “0” when the Cell dies.

RFQMR is capable of altering this potential, to achieve cellular control.

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RFQMR Treatment ProcessRFQMR Treatment Process

RFQMR treatment procedure starts with a conventional Diagnostic MRI.

The Radiologist Prepares the Planning film positioning the RFQMR guns around the region of interest (ROI)

He also does the surface marking of the ROI A template is made from the surface markings The Planning film is fed into the Cytotron Machine,

that calculates the required dose. Thereafter the exposure continues for the determined

period.

Shreis Health Inc. Proprietary & ConfidentialPlanning film

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Typical Dose Planning ProcessTypical Dose Planning Process

•The Gun emission depends on the tissue that come in the gun path.

•Air is the best friend and Fat is the worst enemy of RFQMR.

•PD or Proton Density is simply the H2 atom concentration in a given tissue.

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CANCER PROJECTCANCER PROJECT

Phase-1 Terminal cancer Not amenable to Surgery/ RT/ CT Single lesion Pain alleviation

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CriteriaCriteria

Clinical assessment Radiological assessment Tumor markers Histopathology QOL

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Case- 1Case- 1

Mr R,68 yrs Nov-2003-Ca Lung RLL T2N0 (Adeno ca)

Chemo – (Carbo + Eto) 3 # till March 2004 April 2004 – Prog of disease (vide CT) Presented – Cough Hemoptysis

- Breathlessness

- Pallor

- Debility

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Case 1Case 1

RFQMR-1#26/11/2004 – 09/12/2004

2# 24/12/2004 – 07/1/2005 CT – Jan 2005 – Aug 2005 - Static Now - No Complaints

- Energetic

- Walks 30 m daily

- Appetite Good

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Pre-exposure

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Post-exposure

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Post-exposure

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Post-exposure

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Brain tumoursBrain tumours

Brain tumours: initial results are encouraging

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CASE 2CASE 2

Mr R, 56yrs Nov 2004 – MRI Brain = Left frontal SOL

(4 x 4 x 3 cm)

- SX = Craniotomy x decompression of insular glioma

HPR = Glioblastoma Grade IV RT – 60 Gy/30 # till Jan 2005 CT – Temedol x 2 # till Feb 2005

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Presented Feb 05

- Loss of memory

- Apathetic

- Hemiparesis ® (power3/5) Today after 1 course of RFQMR

- No focal/Gen Neuro deficit

- Normal higher functions and back to work.

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Pre-exposure

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Pre-exposure

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Post-exposure

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Post-exposure

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CASE 3CASE 3

Mr RG, 5yrs May 2004 – Right Hemiparesis with ICSOL - MRI – Left Thalamic glioma with systi

changes obst. Hydrocephalus - Op n = Right VP shunt - Neuro improvement Jun 2004 – Neuro deterioration - Op n = Revision of VP shunt .

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At Presentation – Nov 04

- ® Hemiparesis

-Headache

-Diplopia

RFQMR – Nov 2004

Today - No increase ICT

- Mild residual ® Hemiparesis

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Pre-exposure

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Pre-exposure

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Post-exposure

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Post-exposure

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Pre-exposure

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CASE 4CASE 4

Mr D, 44yrs Sept 2003-SOJ (Se Bil=4.5, AlkPO4=450 BX of pre-op lesion = PD Adeno Ca Nov 2003-Op n-Inoperable mass head

pancreas (1”) -Infiltrating SMR/PV =>Palliative-C cys J +GJ Chemo – gemcit 5# Presentation – Cachexic - Wt loss 20 Kg

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RFQMR-1# 01Jan – 31 Jan 2005

-2# 15Feb – 28 Feb 2005

CT scans –

Sept 2003 – Jan 2005 = Progress of Lesion

Jan 2005 – Sept 2005 = static

Went back to Duty- April 05

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Pre-exposure

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Pre-exposure

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Post-exposure

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CA 19-9CA 19-9

18.5 – > 13.8– > 13.7– > 13.8– >13.7

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CASE 5CASE 5

Mrs NK – 41 Yrs Ca Ovary III C Sx – Jul 03- Sub optional debulking

- Jan 04- Sub optional debulking Chemo- Post operative x02 complete course HPE - Mucin Secreting Adeno Ca Oct 04 – Slowly increasing cyst behind bladder

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RFQMR- Nov 04 Expl Lap - 13.04.05

- Solid intra abdominal masses

- 10 Cm cyst from bladder

- Partial cystectomy HPE - Mesothelial Cyst

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Our experiences with cancer Our experiences with cancer treatmenttreatment

An Overview

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Spectrum of PatientsSpectrum of Patients

30%

18%15%

9%

8%

8%

12%

Brain

Gynae

Hepatobiliary

Upper GI

Lung

Colorectal

Misc

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Overall OutcomeOverall Outcome

66%

34%

Survived

Died

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Survival PeriodSurvival Period

0

10

20

30

40

50

60

70

80

Surviving

> 3 months

< 3 months

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CNS Tumours: Outcome CNS Tumours: Outcome

59%

41%

Survived

Died

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Survival Period: CNS Survival Period: CNS TumoursTumours

0

10

20

30

40

50

60

70

80

90

Surviving

< 3 months

> 3 months

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Evaluation CriteriaEvaluation CriteriaCNS Tumours : OverallCNS Tumours : Overall

02468

10121416

18

LOC Speech MusclePower

Gait Memory

Yes

No

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Evaluation CriteriaEvaluation CriteriaCNS Tumours Localised CNS Tumours Localised

(N=13)(N=13)

0

2

4

6

8

10

12

LOC Speech MusclePower

Gait Memory

Yes

No

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Evaluation CriteriaEvaluation CriteriaCNS Tumours Disseminated CNS Tumours Disseminated

(N=9)(N=9)

0

1

2

3

4

5

6

7

8

LOC Speech MusclePower

Gait Memory

Yes

No

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Cancer Treatment ResultsCancer Treatment Results

0

20

40

60

80

100

Surviving SymptomaticRelief

Back to Work

Treatment Result Criterion

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Potential AppliationsPotential Appliations Diabetes Angiogenesis Tinnitus Macular Degeneration Nanoporation Delivery of Genetherapy Nanoblasting


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