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Musculoskeletal Ultrasound: Diagnosis, Interventions,
Evidence and Applications to Cycling
2014 Medicine of Cycling ConferenceJohn Hill, DO, FAAFP, FACSMProfessor, University of Colorado
Saturday, August 23, 20142:30-3:30 PM
Disclosure Statement
Newton Shoes: Physician Advisory Board
MuscleSound: Inventor Physician advisor/shareholder:
Device & software development using ultrasound to determine muscle glycogen content.
MuscleSound, LLC; US Patents 8,512,247, 8,517,942 and additional patents pending
Objectives
Discuss uses of MSK ultrasound related to the shoulder and hip
Review scientific evidence related to diagnostic and interventional applications
Describe the importance of skeletal muscle glycogen content in cycling
Discuss a new application of ultrasound which can quantify muscle glycogen content and the results of recent validation study.
Objectives
1. Are guided injections Clinically Valid?
Remember…
Injections, whether image guided or palpation guided, require skill
Inherent differences amongst physicians regardless of level of training or experience
Mastery of a skill cannot be assessed by a simple number
No strict definition of accuracy Damage to / injection of
surrounding structures Number of attempts
Confirmation method MRI Fluoro
Needle placement ? Contrast?
Ultrasound Dissection Arthroscopy
Cadaveric model vs. clinical setting
Clinical response?
EFFICACY THE PAINFUL SHOULDER
Multiple studies Multiple indications Mixed results Most favor image guidance
regarding short term improvements in pain and function
Three systematic reviews Two felt there was adequate
evidence of increased improvement in pain and function at 6 weeks to recommend USG
One acknowledged increased accuracy with USG, But did not find clear evidence of
efficacy to justify increased cost Conclusion appeared heavily biased by
one study
Sage, W., et al.,. Rheumatology (Oxford), 2012.Soh, E., et al., . BMC Musculoskelet Disord, 2011. 12: p. 137.Bloom, J.E., et al., . Cochrane Database Syst Rev, 2012. 8: p. CD009147.
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ACCURACY GLENOHUMERAL JOINT
Palpation Guided Cadaveric model,
50% - 96%
Clinical setting 10% - 100%
Non-targeted structures injected Biceps tendon Rotator cuff ACJ Subacromial
Image Guided (Sonography) Cadaveric model
93% Clinical Setting
97% - 100%
Maffulli, N., et al.,High volume image guided injections for the management of chronic tendinopathy of the main body of the Achilles tendon. Phys Ther Sport, 2012.Sethi, P.M. and N. El Attrache, Accuracy of intra-articular injection of the glenohumeral joint: a cadaveric study. Orthopedics, 2006. 29(2)Rutten, M.J., et al., Glenohumeral joint injection: a comparative study of ultrasound and fluoroscopically guided techniques before MR arthrography. Eur Radiol, 2009. 19(3): p. 722-30.
ACCURACY ACROMIOCLAVICULAR JOINT
Palpation Guided Cadaveric model
40% - 72% Clinical setting
39% - 50%
Sonographically Guided Cadaveric model
90% - 100% Clinical setting
100%
-Peck, E., et al., Accuracy of ultrasound-guided versus palpation-guided acromioclavicular joint injections: a cadaveric study. PM R, 2010. 2(9): p. 817-21.-Wasserman, B.R., et al., Accuracy of Acromioclavicular Joint Injections. Am J Sports Med, 2012.-Sabeti-Aschraf, M., et al., The infiltration of the AC joint performed by one specialist: ultrasound versus palpation a prospective randomized pilot study. Eur J Radiol, 2010. 75(1): p. e37-40.
ACCURACY BICEPS TENDON SHEATH
Palpation only accuracy Marker placed Confirmed with sonography 5% (0 – 12%)
Palpation vs US guided Type 1 (only in tendon sheath)
Palpation 27% USG 87%
Type 2 (inside sheath, but also tendon and surrounding area) Palpation 40% USG 13%
Type 3 (only outside tendon sheath) Palpation 33% USG 0%
-Gazzillo, G.P., et al., Accuracy of palpating the long head of the biceps tendon: an ultrasonographic study. PM R, 2011. 3(11): p. 1035-40.-Hashiuchi, T., et al., Accuracy of the biceps tendon sheath injection: ultrasound-guided or unguided injection? A randomized controlled trial. J Shoulder Elbow Surg, 2011. 20(7): p. 1069-73.
ACCURACY HIP Palpation Guided
Cadaveric model 60% - 80% Contacted femoral nerve 27% of
anterior attempts Clinical setting
51% - 78% Sonographically Guided
Cadaveric model 97%
Clinical setting 100%
-Leopold, S.S., V. Battista, and J.A. Oliverio, Safety and efficacy of intraarticular hip injection using anatomic landmarks. Clin Orthop Relat Res, 2001(391): p. 192-7.-Kurup, H. and P. Ward, Do we need radiological guidance for hip joint injections? Acta Orthop Belg, 2010. 76(2): p. 205-7.-Pourbagher, M.A., M. Ozalay, and A. Pourbagher, Accuracy and outcome of sonographically guided intra-articular sodium hyaluronate injections in patients with osteoarthritis of the hip. J Ultrasound Med, 2005. 24(10): p. 1391-5.-Levi, D.S., Intra-articular hip injections using ultrasound guidance: accuracy using a linear array transducer. PM R, 2013. 5(2): p. 129-34.
EFFICACY BENEFIT OF DIAGNOSTIC INJECTIONS
Identify the pain generating structure with accurately placed LA injection
Optimize conservative treatment plan
Pre-surgical planning Theoretically
Improve patient outcomes Decrease cost associated with
“wrong” treatments including PT Injections Surgery
Routinely performed at some institutions
Accuracy appears key Role in evaluation and
management of MSK conditions needs to be further defined
SUMMARY
Image guidance increases the accuracy rate of peripheral joint and soft tissue injections
Injections are a skill, and accuracy rates are variable, even with image guidance
General efficacy appears to improve with image guidance, but this is not the correct outcome to pursue
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Objectives
2. Is Diagnostic MSK Ultrasound Sensitive and
Specific?
EFFICACY BENEFIT OF DIAGNOSTIC INJECTIONS
Identify the pain generating structure with accurately placed LA injection
Optimize conservative treatment plan
Pre-surgical planning Theoretically
Improve patient outcomes Decrease cost associated with
“wrong” treatments including PT Injections Surgery
Routinely performed at some institutions, why not ALL institutions?
Accuracy is the key Role in evaluation and
management of MSK conditions must be precisely defined
SHOULDER PAIN 33 y/o Female
Pain on in off for years in right shoulder No acute trauma
Pain is getting worse
Physical findings +Hawkins, +Neers, +Speeds,
+/- O Brien’s
X-Ray Normal GHJ, Mild ACJ DJD
Prior Treatments Rest, NSAIDS, PT, Subacromial bursa inj X 1
SHOULDER PAIN 33 y/o Female
Working Dx – Rotator cuff syndrome Tendinopathy or Tendon tear?
Full or partial thickness tear?
Which tendons are involved?
Failed standard treatments PT? What kind of PT?
Injection? What was really injected?
Advanced (soft tissue) imaging appropriate MRI?
MR Arthrogram?
Role of US?
Rotator Cuff Ultrasonography
Long history - 1977
• Accumulated research • Meta-analysis, systematic reviews • Performance – MRI, MRI-Arthro, Surgery
Type SEN SPEC
FT-RCT >90% >90%
PT-RCT 60-75% >90%
(MRI 64%/MR arthro 86%) Smith, et.al. Clin Rad 2011
Kelly, et.al. Semin Roentgenol 2009;
DeJesus, et.al. AJR 2009
Best way to Diagnose a Suspected Rotator Cuff Tear?
Meta analysis of 38 cohort studies for U/S(evidence B)
MSK U/S used to evaluate both suspected full & partial thickness rotator cuff tears
Compared with: Clinical Exam MRI Arthrography MR arthrography
Diehr, et.al. J Fam Med, 55,7, July 2006
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Best way to Diagnose a Suspected Rotator Cuff Tear?
Diehr, et.al. J Fam Med, 55,7, July 2006
Test SN SPClin Ex
0.9 0.54
U/S 0.87 0.96MRI 0.89 0.93Arth 0.50 0.96MR Arth
0.95 0.96
Test SN SPClin Ex
N N
U/S 0.67 0.94MRI 0.44 0.9Arth N NMR Arth
In In
Full Thickness Tear Partial Thickness Tear
Supraspinatus Tendon
Instruct patient to place their arm in INTERNAL rotation
Place hand in back pocket (Long axis)45 degrees Coronal/
Sagittal
SST WNLSST Normal Long Axis view
Supraspinatus Tendon
Instruct patient to place their arm in INTERNAL rotation
Place hand in back pocket (Long axis)45 degrees Coronal/
Sagittal (Short axis) 90 degrees Rotation of
long axis
SST WNLSST with Tendinopathy
Supraspinatus Tendon
Instruct patient to place their arm in INTERNAL rotation
Place hand in back pocket (Short axis) 90 degrees Rotation of
long axis
SST Short Axis WNLSST, internal shoulder rotation SA view
Supraspinatus Tendon-Long Axis
Subacromial Bursa
Supraspinatous, birds beak view (insertion)
GT
Supraspinatus Tendon-Short Axis
WNL
SAB
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SHOULDER PAIN 33 y/o Female
Calcific Tendinopathy
Full thickness tearPartial thickness tear
Normal
SHOULDER PAIN 33 y/o Female
Partial thickness bursalsided tear
Counseling
USG SAB injection
Rehab scapula stabilization
Clinical follow-up
Smith, T.O., et al. (2011). “Diagnostic accuracy of ultrasound for rotator cuff tears in adults: a systematic review and meta-analysis.” Clin Radiol 66:1036-48
Management and outcome of this shoulder will be different
SHOULDER PAINFull Thickness Tear
Ultrasound accurately identifies Extent of retraction (to acromion)
Tear size A-P width (# tendons)
Ferri AJR 05; Teefey JBJS 04; Nazarian Radiology 13
Full thickness tearNo tear, mild tendinosis
Non-Invasive Glycogen Measurement: The Next Frontier of Sports
Performance in Cycling
Quantification of glycogen content in a non-invasive way
Hill, JC and San Millan, I. Validation of Musculoskeletal Ultrasound to Assess Muscle Glycogen Content. A Novel Approach. 2014, Phys & SpMed,Submitted
What is Glycogen?
• Glycogen is the storage form of glucose.
• Glucose is the most important form of carbohydrate used by humans, and is an essential fuel source for the body.
• Fat and glucose are the predominant fuels for humans.
• During exercise and competition, glucose is the most important fuel for the muscles.
What is Glycogen?
• Fat storage is unlimited….glycogen storage is VERY LIMITED!
• Glycogen is stored in muscles and liver.
• Maximal Glycogen storage capacity in muscles and liver is about 1.1-1.3 lbs, equivalent to approximately 90-120 minutes of physical activity.
• Maintaining adequate Glycogen content is crucial, especially in athletic performance.
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Importance of Glycogen Storage
Glycogen
Muscle
Glucose
Liver
Glycogen is thestorage form of
glucose in liver and skeletal muscle
Importance of Glycogen Storage
Glycogen
Muscle
Glucose
Liver
During exercise, skeletal muscle uses
glucose deliveredfrom the liver as wellas from the glycogen
storage in muscle.
Glycogen Depletion During Exercise(Muscle Biopsy)
Before
Optimal Levels
After
Glycogen Depletion
Glycogen Will Be Utilized During Exercise Very Rapidly!
As soon as 80 minutes!
Hermansen L, Hultman E, Saltin B. Muscle glycogen during prolonged severe exercise. Acta Physiol Scand. 1967 Oct-Nov;71(2):129-39.
Multiple scientific studies show the direct relationship between glycogen levels and
performance
Bangsbo J, Graham TE, Kiens B & Saltin B (1992). J Physiol 451,205–227Bergström J, Hermansen L, Hultman E & Saltin B (1967). Acta Physiol Scand 71, 140–150Costill DL, Pascoe DD, Fink WJ, Robergs RA, Barr SI, Pearson D. J Appl Physiol, 1990; 69: 46-50.San Millán I, González-Haro C, Hill J. Med Sci Sports Exerc, 2011; 43: S48
The relationship of muscle glycogen content, work time and dietary carbohydrate intake (adapted from Borgström et al. 1967).
Glycogen and Performance
Time to Exhaustion
Bergström J, Hermansen L, Hultman E & Saltin B (1967). Acta Physiol Scand 71, 140–150
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Glycogen Intake and Performance
Bergström J, Hermansen L, Hultman E & Saltin B (1967). Diet muscle glycogen and physical performance. Acta Physiol Scand 71, 140–150
Glycogen Storage and Performance
Bergström J, Hermansen L, Hultman E & Saltin B (1967). Diet muscle glycogen and physical performance. Acta Physiol Scand 71, 140–150
The Importance of CHO and Gycogen Storage
Muscle Glycogen depleted
glycogen glycogen
Muscle with plenty of glycogen
The Importance of CHO and Gycogen Storage
Muscle Glycogen depleted
FAT
glycogen
Muscle Protein(BCAA’s)
During High Exercise intensities(Competition, hard training)
The Importance of CHO and Gycogen Storage
Muscle Glycogen depleted
glycogen
Catabolism Z-Lines
Sarcomere
Muscle Damage Low glycogen levels during hard training and competition will not onlydecrease performance but will also cause muscle damage!!!
Normal Muscle
Damaged Muscle
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Z-Lines
Sarcomere
Muscle Damage Damaged muscle impairs proper muscle glycogen storage capacity!!...This may create a vicious cycle and lead to overtraining!.
Impaired muscle glycogen resynthesis after eccentric exercise. Costil, DL., et al.,J Appl Physiol69: 46-50, 1990
To maintain glycogen storages it is recommended tohave a daily intake of CHO of 6-9g/CHO/Kg
However…Glycogen content can vary among individuals
Nutritional study with Professional Cyclists
4.3 4
6-10
0
1
2
3
4
5
6
7
8
Professional Cyclists Normal Population Recommended Cyclist
CHO
/Kg/
Day
Mean Carbohydrates/Kg/Day
Nutritional study with Professional Cyclists
Even they have a low CHO diet!!
San Millán I, González-Haro C, Hill J. Med Sci Sports Exerc, 2011; 43: S48
We measure the level of gasoline in the tanks of our cars all the time, right?
Glycogen is the Gasoline of our MusclesWhy Don’t We Measure the Gasoline Levels
in Our Muscles?
What if we could?
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It is possible…But…up until now the only way to measureglycogen levels was by a MUSCLE BIOPSY
Traditional Muscle Biopsy Techniques
Invasive and aggressive
Impractical and notclinically applicable
Open Technique
Borgström Technique
Bergstrom, J. Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest. 1975 Nov;35(7):609-16
Through high frequency ultrasound we can assess muscle glycogen content in a rapid, non-
invasive method in about 15 seconds!
Dr. John Hill measures the glycogen levels of Garmin-Transitions Tour de France cyclist Christian Van de Velde.
Glycogen Measurement: Performance Advantages
• If an athlete’s glycogen levels could be tested before, during and after competition, you can ensure the athlete is performing with a full energy stores.
• It would be possible to control the nutrition of the athlete to a level that has never been done before.
• If the athlete does not respond to diet changes, this could be an early method for detecting over training.
Measuring Muscle Glycogen: Does it Work?
• January 2010 – Dr’s. John Hill and Inigo San Millan developed an ultrasound technique to detect changes in muscle glycogen content with ultrasound.
• This same method was applied during the 2010 Tour of California to help the Garmin riders improve their performance, and win the Tour.
• In June 2014, Dr. San Millan and I completed the validation study comparing muscle biopsy to ultrasound. This is the first report of that study
How does it Work?
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Graphic representation of ScanGraphic Views of Muscle Glycogen
Content with Ultrasound
Glycogen stores empty
When glycogen leaves the tissue
It takes water with it
Glycogen stores full
Graphic Views of Muscle Glycogen Content with Ultrasound
Numerical values for each boxNumerical values glycogen partially depleted
Graphic Views of Muscle Glycogen Content with Ultrasound
Further depletion of glycogen Glycogen stores almost empty
Graphic Views of Muscle Glycogen Content with Ultrasound
Over time total numerical value
Drops as glycogen is depleted
Software design can process just the
Key elements and exclude the artifact
Graphic Views of Muscle Glycogen Content with Ultrasound
These past slides demonstrate graphically how the subjective ultrasound image is converted to an objectivenumerical value which anyone can understand
Connective tissue is a critical artifactWhich can be digitally subtracted
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Garmin Cyclist before and after Maximal Exertion (V02 test)
Pre-exercise cross section of
Rectus FemorisPost-exercise same muscle
Garmin Cyclist at Baseline and after 4hour hard training ride
Baseline hypoechoic (dark)
muscle appearance
After 4 hour ride, glycogen is partially depleted but not as much as after VO2test because the rider is able to eat and continue replacing glycogen stores
Novel Methodology for Muscle Glycogen Content Assessment through High Frequency Ultrasound
How are the Images Processed?Baseline Rectus Femoris SA Post-Exercise Rectus Femoris SA
Same exact muscle after 90 minutes of moderately intense exertion on cyclergometer
How are the Images Processed?
Original Baseline RF LA view Original Post Ex RF SA view
MuscleSound, LLC; US Patents 8,512,247, 8,517,942 and additional patents pending
How are the Images Processed?
Baseline RF LA view Post-Exercise Rectus Femoris SA
-Chrome is cropped, leaving only the ultrasound image
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How are the Images Processed?Baseline RF LA view Post-Exercise Rectus Femoris SA
-Sides are cropped, image is smoothed using Gaussian blur
How are the Images Processed?Baseline RF LA view Post-Exercise Rectus Femoris SA
-Thresholding; converting to binary image (black and white)
How are the Images Processed?Baseline RF LA view Post-Exercise Rectus Femoris SA
-Morphing technique to fill in holes which connects all muscle-Image is returned to Gray Scale
How are the Images Processed?
Baseline RF LA view Post-Exercise Rectus Femoris SA
-Image extraction performed which removes skin and fat-Bottom crop removes connective tissue and artifact-Pixel intensity of all connective tissue is 255-Muscle glycogen score is determined from Pixels with 1-254 intensities
How are the Images Processed?
Combined SA & LA , Rectus Femoris 3 Different Scans of RF SA view
-Pixels are averaged and compared across linked images, -This allows individual scans to be tested for consistency and reliability-Pixel intensity is changed from 0-255 to 0-100 which simplifies the interpretation (Entire process takes
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Methods 22 male competitive cyclists, Pro, Cat 1-4
Perform steady state cyclergometer test for 90 minutes at mod-high exercise intensity CHOox of 2-3 gm/min Lactate levels, 2-3 mM
Age Height Weight % Body
Fat*
BMI #
Races/yea
r
31.3 +/‐
5.1
183.7 +/‐
4.9 cm
76.8 +/‐7.8
kg
12.1+/‐
2.4 %
22.7 +/‐
1.8
27.1 +/‐
19.7
Methods
Pre- and Post-exercise glycogen content of right and left Rectus Femoris was measured using: Histochemical analysis through muscle biopsy
High frequency ultrasound scans using MuscleSound® technology to measure and quantify glycogen
Muscle Biopsy Technique
Why rectus femoris muscle rather than the vastus lateralis? Less connective tissue reduces potential artifact in
the ultrasound images Less connective tissue in the muscle biopsy samples
Reducing potential artifacts may improve both sensitivity and specificity
More precisely detect changes in muscle glycogen content Many competitive cyclists believe the RF region of the
quadriceps feels empty and fatigued before VL region
Muscle Biopsy Technique
Ultrasound guided muscle biopsy Precisely directs biopsy
Color flow Doppler Avoid vascular structures
No complications were encountered with 88 consecutive biopsies No hematoma No hemorrhages
Hill, JC and San Millan, I. Validation of Musculoskeletal Ultrasound to Assess Muscle Glycogen Content. A Novel Approach. 2014, Phys & SpMed, Submitted
Muscle Biopsy Technique
Bard MonoptyDisposable Core Biopsy Instrument (Liver biopsy) 12 gauge X 10 cm length
biopsy needle 2 passes made at Baseline
and Post-exercise
Correlation Results
Hill, JC and San Millan, I. Validation of Musculoskeletal Ultrasound to Assess Muscle Glycogen Content. A Novel Approach. 2014, Phys & SpMed, Submitted
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Correlation Results
Hill, JC and San Millan, I. Validation of Musculoskeletal Ultrasound to Assess Muscle Glycogen Content. A Novel Approach. 2014, Phys & SpMed, Submitted
Correlation Results
Hill, JC and San Millan, I. Validation of Musculoskeletal Ultrasound to Assess Muscle Glycogen Content. A Novel Approach. 2014, Phys & SpMed, Submitted
Individual Subjects Change
Muscle Biopsy Glycogen Change Ultrasound Glycogen Change
Hill, JC and San Millan, I. Validation of Musculoskeletal Ultrasound to Assess Muscle Glycogen Content. A Novel Approach. 2014, Phys & SpMed, Submitted
Correlation of Different Muscles
Hill, JC and San Millan, I. Validation of Musculoskeletal Ultrasound to Assess Muscle Glycogen Content. A Novel Approach. 2014, Phys & SpMed, Submitted
Correlation of Different Muscles
Hill, JC and San Millan, I. Validation of Musculoskeletal Ultrasound to Assess Muscle Glycogen Content. A Novel Approach. 2014, Phys & SpMed, Submitted
Conclusions of Validation Study
Pre- and post-exercise ultrasound scans using MuscleSound® technology were highly correlated with histochemical glycogen assessment through muscle biopsy.
Changes in glycogen content from pre- and post-exercise were also highly correlated between MuscleSound® technology and muscle biopsy histochemical analysis.
Hill, JC and San Millan, I. Validation of Musculoskeletal Ultrasound to Assess Muscle Glycogen Content. A Novel Approach. 2014, Phys & SpMed, Submitted
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Conclusions of Validation Study
Results show that the use of high-frequency ultrasound through MuscleSound® technology Accurate and reliable method to measure skeletal
muscle glycogen It is practical, rapid and non-invasive.
Hill, JC and San Millan, I. Validation of Musculoskeletal Ultrasound to Assess Muscle Glycogen Content. A Novel Approach. 2014, Phys & SpMed, Submitted