Post on 28-Dec-2015
Single Voxel MR Spectroscopy in Non-Herniated Painful, Herniated Painful, and Non-Painful Lumbar Discs
L Tanenbaum1, S·Hu2, M·Gornet3, S·Berven2, J·Peacock4, J·Lotz2,4, D·Bradford4,·J Claude4, P·Kane4, F·Schranck3, D·Stewart5
1Icahn School of Medicine at Mount Sinai, 2University of California San Francisco, 3Orthopedic Center of Saint Louis, 4Nocimed, LLC,
5MRI Partners of Chesterfield1
PG
Lactate
col
Disclosures
• Tanenbaum, L: Nocimed, LLC - advisory board• Bradford, D; Lotz, J: Nocimed, LLC - management,
shareholder, royalty• Kane, P; Claude, J: Nocimed, LLC - shareholder,
consulting• Peacock, J: Nocimed, LLC - management, shareholder• Schranck, F; Gornet, M: The Orthopedic Center of St.
Louis - Nocimed sponsored research grant, Nocimed, LLC - shareholder
2
Purpose
3
• Evaluate non-invasive in vivo single voxel MR spectroscopy (SVS) in lumbar discs on two commercial 3T scanners - GE Signa & Siemens Verio for
a) discogenic low back pain (LBP) pain patients receiving provocative discography (PD), and
b) asymptomatic control volunteers (ASY) • Correlate results to clinical phenotypes– non-herniated painful (NHP)– herniated painful (HP)– non-painful (NP) discs
BackgroundDisc degeneration
• altered disc structure and biochemical composition that may or may not cause pain– decreased proteoglycan synthesis– increase matrix catabolism
• features that differentiate painful from non painful degenerative discs not well understood.
*Buser, 2010 Spine: Affiliated Society Meeting Abstracts
• consistent changes in markers of hypoxia, innervation and inflammation showed strong correlation with discs associated with pain
*Buser, 2010 Spine: Affiliated Society Meeting AbstractsNucleus samples
Gene expression with highest correlation between painful vs. non-painful discs relate to (R2=.67):
1. hypoxia - lactate dehydrogenase; 2. innervation - nerve growth factor.
*Buser, 2010 Spine: Affiliated Society Meeting Abstracts
BackgroundDisc degeneration
• Painful discs are distinguished by hypoxia, inflammation, neovascularization & neoinnervation*
• Consistent changes in biomarkers/chemical mediators detectable and quantifiable with MR spectroscopy
*Freemont, A. J., (2009) Rheumatology; 48:5–10.
BackgroundIdentifying the painful disc
Background-Ex vivo Disc SVS, 11T HR MAS Surgical Samples – PG/LA
PG
Lactate
col
Painful Disc(PD+, LBP)n=9
PG
Lactate
col
Non-Painful Disc(Scoliosis)n=9
8
Keshari, Spine 2008. 33(3): p. 312-317
p<.005
Materials & Methods
• Iterative technical development protocol– Conducted in series: GE (2008-10), Siemens (2011-13)– T1/T2 weighted imaging sequences– SVS acquisition, each lumbar disc sequentially• Inter-platform differences:
– OVS bands: GE only (not used for Siemens)– Autoshim Auto + Manual shim: Siemens protocol refinement
– Manual voxel localization in disc to remove end-plates
9
Materials & Methods• Acquisition Systems – GE Signa HDxt 3.0T, v14x
• HDCTL 456 spine coil• Pulse Sequence: custom Chess/Press
– “modified” PROSETM for disc SVS: TR=1500, TE=28ms
– Siemens 3T Verio, Model 10276755 Numaris/4 • Spine Coil Model 8622743• Pulse Sequence: SVS Syngo VB17 Version 1.0
– investigational “patch” for 3-5mm voxel height
• Both single center, Nocimed sponsored, IRB approved– GE 3T: University of California at San Francisco– Siemens 3T: The Orthopedic Center of St. Louis
10
Non-Painful Disc
Non-Painful
Materials & Methodssignal post-processing
Automated Channel Select Frame Edit Phase/Freq Apodize Aggregate Baseline
11
Materials & Methodstechnical “success” & signal quality assessment
12
• GE data: initial in vivo development cycle of entire approach• Reported data not include technical failures for poor signal quality• Technical “failures” = only “indeterminate” results of Dx correlation
algorithm
• SIEMENS data: x-platform application/refinement of prior learning • Less technical development required• Reported data includes all completed acquisitions - signal quality
successes & failures• Primary Signal (satisfactory) Quality Assessment Criteria:o SNR > 3 for PG or LA peak regionso Water FWHM < 35 Hzo Presence (fail) or Absence (accept) of lipid motion artifact
• Different approach per platform, serial development phases• Earlier GE platform data:
– Multi-variate (PG & LA) automated statistical algorithm development via “JMP” logistic regression software
– Predictive value of SVS biomarker measures for painful vs. non-painful
• Later Siemens platform data:– Simple PG/LA ratio– Predictive value/statistical modeling planned
(> more pain patients)
13
Materials & Methodsdiagnostic interpretation/correlation to disc type
1%
99%
1%
14
Materials & Methodsstudy design – inclusion criteria
• Male and non-pregnant females, 18-70 yrs old • Pain group:
– Oswestry Disability Index ≥ 40%, or Visual Analog Scale ≥ 4– Indicated for Lumbar Spine Provocation Discography (PD)
• Practice Guidelines for Spinal Diagnostic and Treatment Procedures (ISIS, 2004)
• PD performed 6wk-6mo before, or 1mo after, Disc SVS exam– Up to 12 mo before in earlier GE study
• Asymptomatic control volunteers:– Absent chronic severe LBP– VAS≤1, ODI≤10.
15
Materials & Methodsstudy design – exclusion criteria
• Complicating extradiscal pain sources– fracture, spondylolisthesis, spondylolysis
• Prior lumbar surgery or intradiscal treatments– except diagnostic provocative or anesthetic
discography• Chronic disease or pain, or psychological
dysfunction, relevant to study objectives
GE studyn= 42 Subjects, 79 Discs1
16
Pain Pts (PD)n=14
Volunteersn=28
Painful Discs(PD+)
Non-Painful Discs(PD-)
Non-Painful Discs(assumed)
n = 15 n = 49
n = 15+ Control, Painful
n = 64- Control, Non-Painful
Siemens studyn=33 Subjects, 130 Discs1
17
Pain Pts (PD)n=14 Volunteers
n=19
Non-HerniatedPainful Discs
(PD+)
HerniatedPainful Discs
(PD+)
Non-Painful Discs
(PD- & remote levels)
Non-Painful Discs
(assumed)
n = 32 n = 9
n = 16 n = 1031
n = 1191
1 Includes n=1 disc excluded from analysis as non-lumbar (S1-S2)2 Includes n=1 disc analyzed separately due to “extra”discal co-morbidities (spondylosis + facet arthropathy)
18
+
-
Results- 3T GE Signa Case 1, Pain Pt (PD+ L5S1, PD- L4L5)
Discogram: +/-
Hu, Orthopaedic Research Society 2010
19
Results - GE 3T Signa 94% (74/79) Determinate, 99% (73/74) Accurate (PG,LA)
Hu, Orthopaedic Research Society 2010
SVS Positive n=13 all true+*
SVS Negative n=60 true-, 1 false-*
SVS Indeterminate n=5
PG &
LA-
rela
ted
Dx
Algo
rithm
“sc
ore”
Case 2 – 3T Siemens VerioNHP Pain Pt, 2-level PD+/-
L5-S16mm
L4-L56mm
L3-L45mm
L2-L35mm
L1-L24mm
10
0
22
Discogram: +/-
Results - Siemens 3T VerioSignal Quality Success 85% (100% Manual Shim, >1mm)
23
Total Autoshim only Auto+Manual Shim0
20
40
60
80
100
120
140
110
74
36
7
6
1
11
10
1
2
2
0
Lipid/motionLow SNR < 3xPoor Shim (WaterFWHM > 35Hz)Success
Technical Success, Signal Quality - Siemens 3T Verio Overall vs. Autoshim only vs. Autoshim + Manual Shim (Later Protocol Rev)
Dis
cs (
#)
Protocol Development (Shim)
Both 1mm Voxels
20%
80%
95%
5%
92 Discs21 Sub-
jects
38 Discs11 Subjects
15%
85%
130 Discs32 Subjects
24
L2L34mm
L1L24mm
Autoshim Only(Fail Water FWHM)
Auto+Manual shim
N313
Asymptomatic Control Volunteer
Results - Siemens 3T VerioAutoshim only vs. Auto+Manual Shim – Example
Conclusionsdisc SVS signal quality - reliability
• 100% robust disc spectra per signal quality criteria @ ≥3mm disc height per later protocol refinements (autoshim + manual shim) of the Siemens 3T platform study
• 80% reliability w/ autoshim only
25
Results – Siemens 3T VerioPG/LA Dx Correlation vs. Disc “Type” Controls (n=110)
26
0 1 2 3 4 50.20
2.00
20.00
Disc SVS PG/LA Ratio vs. Disc Type
log
PG/L
A Ra
tio ,
Lum
bar D
isc S
VS
PD+Non-herniated
PD+Non-herniated,Spondy
PD+Herniated
NC(PD- and ASY)
n=1n=1 n=100n=8
27
Painful Non-Painful0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
93% 100%
7%0%
Mis-Match vs. Control
Match vs. Control
Dx Correlation Results, GE & Siemens 3T Combined(PG & LA-based Dx Algorithms separately developed, MR platform-specific)
Dis
cs (
#)
n=13
n=1
n=161
n=0
Control Disc Type
Combined Siemens & GE 3T ResultsPG & LA correlate 174/175 (>99%) discs, 72 subjects
Conclusions
• Combined PG & LA-related results from the two serial GE & Siemens 3T platform disc SVS development studies reflects >99% correlation between classic “contained” discogenic pain and non-painful discs in 175 total discs in 72 subjects
– 100% PPV for pain in 13 painful PD+ discs
– 0% False+ in 161 non-painful discs
28
Conclusions
29
• Disc SVS may be most appropriate for classic contained axial discogenic low back pain w/o extradiscal pain generators, vs. pain caused by extradiscal morbidities (e.g. herniations, facet, vertebral abnormalities)–may still enhance Dx regimen in multi-factorial cases
involving both intra-discal and extra-discal pain sources
Single Voxel MR Spectroscopy in Non-Herniated Painful, Herniated Painful, and Non-Painful Lumbar Discs
L Tanenbaum1, S·Hu2, M·Gornet3, S·Berven2, J·Peacock4, J·Lotz2,4, D·Bradford4,·J Claude4, P·Kane4, F·Schranck3, D·Stewart5
1Icahn School of Medicine at Mount Sinai, 2University of California San Francisco, 3Orthopedic Center of Saint Louis, 4Nocimed, LLC,
5MRI Partners of Chesterfield30
PG
Lactate
col