CANM 2016 Annual Scientific Meeting 24 Apr 2016
Future of Myocardial Perfusion Imaging: SPECT with CZT R Glenn Wells, PhD Medical Imaging Physicist Cardiac Imaging
Disclosures: Scientific Studies in collaboration with GE Healthcare
Innovations in Cardiac SPECT Software Evolution for Cardiac (GE Healthcare) Flash3D (Siemens) Astonish (Philips) Hardware Wide-beam Reconstruction (UltraSPECT) nSPEED (Digirad) Hybrid-recon (Hermes)
Collimator Modeling
Iterative Reconstruction
*
RR
*
L1
Measured projection data
Object
Calculated projection data
AC
Compare Reconstructed image
Estimate
MAP
Update
L1
Yes
No Converge?
Full-time (FT) vs Half-time (HT) Ali et al, JNM 2009 (Infinia camera) FT No AC (13min) HT No AC (7min)
Stress Rest
Stress Rest
FT AC
Stress
HT AC
Stress
Rest
Rest
Evolution: Clinical Evaluation Half
Normal
Abnormal
Normal
69
5
Abnormal
1
37
Normal
Abnormal
Full
No Corrections
Half Full
Attenuation Correction
Normal
71
2
Abnormal
2
31
106/112 = 95% (k=0.88)
102/106 = 96% (k=0.91)
Ali et al, J Nucl Med, 2009
Software Validation Software
# pts
Time (min)
Evolution
112
7.5/6
Bateman Astonish J Nucl Cardiol 2009
110
6
30
Stress-only
Venero Astonish J Nucl Cardiol 2009
187
8.5/6.7
10/35
Rest/stress
DePuey WideJ Nucl Cardiol 2009 Beam
209
4.5/4.0
9/32
Rest/stress
Kangasmaa HybridNucl Med Comm 2011 recon
30
6.7
19
Rest from rest/stress
Ali
Activity (mCi)
Protocol (time – min)
9.3/28.5 Rest/stress
J Nucl Med 2009
Advances in Camera Technology
Cardius 3 XPO
IQ SPECT CardiArc
Discovery NM 530c
DSPECT
New Hardware for SPECT New Detectors ( NaI -> CZT) More Detectors ( 2 -> 19 ) New Collimators ( Parallel -> Pinhole
Ultra-High Sensitivity Slit-Slat Astigmatic ) [ Cardiac Focused ]
Cameras use CZT – What is CZT? CZT = Cd1-xZnxTe
x typically < 0.2 NaI
CZT (x=0.2)
Density (g/cc)
3.67
5.81
m (cm2/g) at 150keV
0.566
0.544
Zeff
51
50
Intrinsic Efficiency (%)
85 (9mm)
80 (5mm)
So, stopping power of the detectors is about the same; CZT does not increase sensitivity
Camera uses a CZT detector
4cm
16 x 16 pixelated array 2.46 x 2.46 mm pixels = 4 cm x 4cm panel Dedicated ASIC for signal processing Very compact detector allows multiple heads
Focused Collimation Array of 19 pinhole collimators Arranged in 3 axial rows
Focused on the heart “Quality field of view” positioned around the heart
D-SPECT collimation Tungsten parallel hole collimator: with square holes (matching detector elements) 21.7mm x 2.26mm Compare to typical NaI camera with hexagonal holes LEHR: 27mm x 1.22mm LEGP: 24.7mm x 1.4mm 1x4 array of detector panels: 16 x 64 pixels, 4 x 16 cm Gambhir JNM 2009
D-SPECT (Spectrum Dynamics)
9 Detector columns in an arc around the patient Erlandsson, PMB 2009 Slomka, JNC, 2009
Comparing Sensitivity and Resolution
Imbert, JNM, 2012
Standard Gamma Camera Images
Stress Rest CZT Camera Images (1 minute)
Stress Rest CZT Camera Images (2 minute)
Stress Rest CZT Camera Images (3 minute)
Stress Rest CZT Camera Images (4 minute)
Stress Rest
Stress
Rest
CZT vs Infinia: Clinical Concordance
Infinia
Normal
Abnormal
Normal
83
0
Abnormal
4
63
NM530c
No Corrections
Concordance = 97% (146/150 ) (kappa = 0.95)
Ali et al, American Heart Association, 2009
LV volumes and ejection fraction
N=150
Miao, J Nucl Cardiol 2015
SPECT Camera Validation Camera
# pts Time (min)
Dose (mCi)
11/28
vs
Sharir JACC CI 2008
D-SPECT
44
4/2
Full-time
Esteves JNC 2009
NM 530c
168
4/2
Gambhir JNM 2009
D-SPECT
18
4/2
Stnd
Full-time
Maddahi JNC 2009
Cardius / nSPEED
448
5/4 (3XPO)
7-10 / 20-30
Full-time
Buechel EJNMMI 2010
NM 530c
75
3/2
8 / 24
Full-time
Sharir JACC 2010
D-SPECT
238
4/2
10/30
Full-time
Corbett SNM 2010
IQ-SPECT
54
4
Stnd
Full-time
Songy CNM 2011
NM 530c
153
5
10-15 / Full-time 30-45
3.5 + 1 Full-time (Tl201)
This is the technology Where is it taking us?
NCRP 160: Ionizing Radiation Exposure of USA Population (2009) Collective Radiation Dose (medical imaging) Increased:
124,000 person-sievert (1990) 900,000 person-sievert (2006) Chernobyl nuclear accident = 400,000 person-sievert The average dose per person from medical imaging has increase 6x 0.5 mSv (~ 1982 ) 3.0 mSv (2006) The two procedures that contribute the most to the collective dose are CT exams Cardiac Nuclear Medicine Kostin: 27 Apr 1986
Medical Imaging Radiation Exposure Procedure Myocardial Perfusion Imaging
Avg Eff Ann Eff Dose / % of Total Dose (mSv) Person (mSv) Eff Dose
15.6
0.54
22.1
CT - Abdomen
8
0.446
18.3
CT - Pelvis
6
0.297
12.2
CT - Chest
7
0.184
7.5
38%
Desire to reduce radiation doses Fazel, NEJM, 2009
Lower Time
Lower Dose Almost
Biggest potential difference is Patient motion
Kim et al SNM 2010
Low-Dose SPECT Studies Camera
Nelson
NM ASNC 2012 530c
# pts
Dose (mSv)
Activity (mCi)
Protocol (time – min)
414
3.6
3/9
Rest/Stress 6.5/4.5
DePuey Ventri J Nucl Cardiol 2011
160
6.8
5.7 / 17.5
Rest/stress * 14 / 12
Nkoulou NM J Nucl Med 2011 570c
50
4.6 (+CT)
8.65 / 8.65
Stress / rest 5/5
Duvall NM J Nucl Cardiol 2011 530c
131
5.8
5 / 15
Rest / stress * 5-8/3-5
Gimelli NM Eur J Nuc Med MI 2012 530c * No AC
137 5.10 (m) / 6.12 (w)
5-6 / 10-12
Stress / rest * 7/6
Slomka et al Curr Cardiol Rep 2012
Dose Reduction at UOHI New Technology allows reduction in patient radiation exposure
Can we go further? Less dose + more time? Patient Dose at UOHI: 11 mSv 5 mSv
NM530 rest 190 MBq, 10 min stress 525 MBq, 6 min inconsistencies in projection data with changing activity concentrations -> artifacts and inability to capture rapid kinetics Poor Sensitivity ~ 100x less sensitive than PET
Multiple Views at Once Completely stationary
‘Almost’ stationary Temporal Resolution of 3-10s
Pro/Con of Cardiac SPECT Cameras Focused collimation: Reduced field-of-view Increased sensitivity without loss of resolution Supports higher temporal resolution Multiple detectors No gantry motion = (quasi)stationary Better temporal resolution Improved reconstruction algorithms (resolution recovery, CT-based AC, scatter) Better images from low-count data. Simple Acquisition Protocols use PET tools
Is SPECT good enough? Potential concerns (compared to PET) … Count levels still lower (12 - 25x) Noisier images Ability to do AC ( less so with NM 570c )
Scatter correction with CZT – low-energy tail Resolution still lower greater mixing of compartments and partial volume effects
SPECT tracers vs PET tracers – worse extraction fraction
Dynamic Acquisition Tetrofosmin Time
Time
25
75
35
113
45
55
158
240
65
100 %
480
0%
Stress 30 mCi (1100 MBq), 20s injection, (rest subtracted) 9x10s, 6x15s, 4x120s frames
Is SPECT good enough? Potential concerns (compared to PET) … Count levels still lower (12 - 25x) Noisier images Ability to do AC ( less so with NM 570c )
Scatter correction with CZT – low-energy tail Resolution still lower greater mixing of compartments and partial volume effects
SPECT tracers vs PET tracers – worse extraction fraction
Attenuation Correction with CZT InfiniaHawkeye 4
NM 530c
61 y.o. Male, Normal Wall Motion stress
Standard No AC
rest stress
CZT-No AC rest
stress
Standard AC
rest
stress
CZT-AC rest
Perfusion Score Difference: CZT - Infinia
No Correction
Attenuation Correction
N=108 pts
Pourmoghaddas, JNC 2014
Low Energy Tail Scatter Window
Photopeak Window
1
Normalized counts
0.8
99mTc
photopeak at 140 keV
0.6
0.4
0.2
0 0 20 40 60 80 100120140160180200220240260 Energy (keV)
Pourmoghaddas, JNC 2014
Perfusion Score Difference: CZT - Infinia
No Correction
Attenuation Correction
N=108 pts Scatter Correction
Pourmoghaddas, JNC 2014
Deconvolution Scatter Correction
Kacperski, Phys Med Biol 2011
Is SPECT good enough? Potential concerns (compared to PET) … Count levels still lower (12 - 25x) Noisier images Ability to do AC ( less so with NM 570c )
Scatter correction with CZT – low-energy tail Resolution still lower greater mixing of compartments and partial volume effects
SPECT tracers vs PET tracers – worse extraction fraction
Processing with FlowQuant
Klein R et al, J Nucl Cardiol 2010; 17:600–16
Example Rest processing Measured Bloodpool 9 mCi tetrofosmin Standard bolus injection
Measured Myocardium Fit Myocardium
Klein R et al, J Nucl Cardiol 2010; 17:600–16
Is SPECT good enough? Potential concerns (compared to PET) … Count levels still lower (12 - 25x) Noisier images Ability to do AC ( less so with NM 570c )
Scatter correction with CZT – low-energy tail Resolution still lower greater mixing of compartments and partial volume effects
SPECT tracers vs PET tracers – worse extraction fraction
Extraction and Flow
K1 = E(F)*F
A comparison of K1 measured with SPECT in a pig model to literature values and to PET.
Wells et al, JNM 2014
What is the Evidence that it Works?
Pig in the CZT camera
LAD occluded during stress Microspheres injected for comparison
SPECT MBF Protocol
CT acquired with Hawkeye for AC Infinia Hawkeye-4
Pig Flow – Tetrofosmin
Rest Stress
Wells et al, J Nucl Med 2014
Tetrofosmin K1 (n=8 pigs)
r = 0.67
r = 0.46
Wells et al, J Nucl Med 2014
Sestamibi K1 (n=4 pigs)
r = 0.72
r = 0.83
Wells et al, J Nucl Med 2014
Pig Flow – Tl-201
Wells et al, J Nucl Med 2014
Thallium-201 K1 (n=7 Pigs)
r = 0.82
r = 0.83
No AC for all Tracers gave similar performance to AC Wells et al, J Nucl Med 2014
Human Studies MPR index = K1-stress / K1-rest
CA > 50%
Ben-Haim, J Nucl Med 2013
Human Studies N=23 (multivessel CAD)
CA > 50% FFR < 0.8 Sens. 80% 89% Spec. 85% 82% Acc. 81% 85% N=26 vessels
Bouallègue, J Nucl Med 2015
MPR Index = K1-stress / K1-rest
Human Studies 3.0
N=55 pts
2.5
2 x 1.5 mCi Tl-201
2.0
CA > 50% (left-main) > 75% (vessels) Sens. 86% Spec. 78% Acc. 80%
1.5 1.0 0.5 0 VD
1 VD
2 VD
3 VD or LMD Shiraishi, Circ J 2015
Direct Comparison to PET
vs 82Rb
PET vs Tetrofosmin SPECT
Patients imaged 1- 4 week apart
Comparing SPECT and PET
99mTc-Tetrofosmin
82Rb-PET
Wells, ASNC 2015
Preliminary Data from 9 Patients
R = 0.9
R = 0.8 Wells, ASNC 2015
The Future of SPECT MPI Is Patient-specific protocols using reduced acquisition time and/ or reduced patient dose Dynamic imaging for absolute MBF and MFR
Acknowledgments University of Ottawa Heart Institute Terrence Ruddy Rob deKemp Ran Klein Rob Beanlands Ben Chow
Patti Irvine Brian Marvin Azmina Merani Anna Kim
Lyanne Fuller
Rachel Timmins Karen Soueidan Karen Vanderwerf
ACVS
Corinne Bensimon Lihui Wei Pasan Fernando Daniel Yuan
Julia Petryk
Amir Pourmoghaddas Sarah Cuddy
GE Healthcare Technical support Aharon Peretz Gil Kovalski Jonathan Sachs Adrian Soil
Ontario Research Fund
Questions?
NM 530c Count Rate Performance Observed Count Rate (cps)
Essentially no dead time
350 kcps
CZT Infinia
True Count Rate (cps)
With no deadtime loses
Calculating Flow K1
Tissue Ct(t)
Blood Ca(t)
Measure Cm(t)
k2
K1 = MBF x E(MBF)
AIF Cm (t ) FBV Ca (t ) (1 FBV ) Ct (t )
FBV = fractional blood volume Klein, JNC 2010, 555-70
Tracer-Blood Binding Only tracer in plasma is available for uptake to tissues…
Iida, EJNMMI 2008
Tracer-Blood Binding N=3 pigs (normal) Standard injection of each tracer Blood sampling: 20s for 6 min; 60s to 10min; 120s to 20min; 25, 30, 40, 50 and 60 min Samples centrifuged immediately to separate blood/plasma 16000 g for 15s Radioactivity measured in well-counter to determine whole blood : plasma concentration ratio
Blood-binding curves Blood-binding curves for the three common SPECT tracers
Wells et al, JNM 2014
CZT Energy Resolution g-ray
NaI
g-ray
CZT 140 keV x
e-ee-e40 photons / eV x eee-e- e-ee-e- e- ee-e- e- ee- e-e- e1-3 e- / 10 photons e-ee- eee-e- e- e-e- e- eee-e- e-e-e- e- e- ee-ee-ee-eeeee-e- e-ee-e- e-e-e- ee-e- e- eeee-ee-e- e- e-e- e-e- ee- e-e- ee-e- e- ee- ee-ee- ee-e- e- e-e- e-e-ee-e-e- e- e-e- e- ee- e- e-e- e-e- e-ee- e- ee-e-e- e- e~ 1,000 e~31,000 eBand Gap = 1.55 eV 3% < 0.5% 4.5 eV / e-
Extrinsic Energy Spectra – NM 530c Potential for scatter reduction
Tc-99m FWHM Infinia 9.5% CZT
5.8%
Pig Protocol ~30-40 kg farm bred pigs – female Yorkshire cross Animals anaesthetized ( telosol/thilazol + isoflurane) Thoracotomy Catheter to left atrium for microsphere injection Suture just below D2 of LAD on drawstring Catheter to
ear for tracer injection opposite ear for fluids, persantine, etc. leg (femoral artery) for blood withdrawal
Dose Reduction vs MBF
Timmins, SNM 2014
Low Dose Pig Studies Full
Half
1/8
Tetrofosmin
Sestamibi
Thallium
Timmins, Med Phys, 2015b
