SPECT/CT Basics, Technology Updates, Quality Assurance, and Applications

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SPECT/CT Basics, Technology Updates, Quality Assurance, and Applications S. Cheenu Kappadath, PhD Department of Imaging Physics University of Texas M D Anderson Cancer Center, Houston, Texas skappadath@mdanderson.org

Educational Objectives 1. Understand the underlying principles of SPECT/CT image acquisition, processing and reconstruction 2. Understand current and future clinical applications of SPECT/CT imaging 3. Familiarization with commercially-available SPECT/CT systems

Outline Review of SPECT principles Iterative SPECT reconstruction Hybrid SPECT/CT imaging SPECT/CT quality assurance Commercial SPECT/CT systems SPECT/CT clinical applications

SPECT Basics Single Photon Emission Computed Tomography Radio-pharmaceutical administration injected, ingested, or inhaled Bio-distribution of pharmaceutical uptake time Decay of radionuclide from within the patient the source of information Gamma camera detects gamma rays and images (tomography) the radio-pharmaceutical distribution within the patient SPECT Used for visualization of functional information based on the specific radio-pharmaceutical uptake mechanism

SPECT Hardware Anatomy of a Gamma camera 1. Collimator 2. Scintillation Detector 3. Photomultiplier Tubes 4. Position Circuitry 5. Data Analysis Computer U of British Columbia

SPECT Back-Projection Model g(s, ) = f(x,y) along an in-plane line integral Bruyant, P. P., J Nucl Med 2002; 43:1343-1358

Crystal Thickness Thinner crystals spatial resolution interactions occur at a better defined depth multiple interactions less likely less light spread interaction likelihood for higher energy s Thicker crystals sensitivity interaction likelihood (esp. for higher E s) likelihood of multiple interactions greater light spread spatial resolution

Spatial Resolution Intrinsic Spatial and Energy Resolution # of scintillation photons, N Gamma-ray energy, E Spatial Resolution = 100 /N 1/ N 1/ E Energy Resolution = 100 FWHM/E 1/ E B L e H Collimator Resolution R g D( Le H B) L e L e System Resolution R R R 2 2 2 s i g D

SPECT Acquisitions SPECT acquires 2-D projections of a 3-D volume Yale School of Medicine SPECT in the year 2000: Basic principles, JNMT 24:233, 2000

Radon transform angular symmetry violated in SPECT P( ) Anterior View P( + ) horizontally flipped Posterior

Radon transform angular symmetry violated in SPECT Why? Due to Differential Attenuation L a i b I( i ) b I( i ) = I 0 e - a (L)dL c I( i + ) = I 0 e - a (L)dL I 0 c Other mediating factors: I( i + ) distance-dependent resolution depth-dependent scatter

SPECT Acquisitions SPECT projections acquired over 360 Exception: Cardiac SPECT acquired over 180 0 0 180

SPECT images have isotropic voxel size 2-D filter of projections 3-D post-reconstruction filter transverse sagittal coronal No volume smoothing Butterworth: 0.6 Nyquist, 10 th order

SPECT Filtered Back- Projection FBP based on ideal Radon inversion formula assumes a linear, shift-invariant system and angular symmetry of projections SPECT imaging systems are neither angularly symmetric nor shift-invariant SPECT projection data affected by attenuation, scatter, and spatial resolution that are all depth-or distance-dependent Thus, FBP reconstruction cannot adequately model the physics of SPECT

Conventional SPECT Corrections Attenuation: Chang post-processing algorithm I(x,y) = SPECT image w/o AC I(x,y, i ) = I AC (x,y).e - L(x,y, i ) I AC (x,y) = I(x,y) / {(1/M). i e - L(x,y, i ) }; i = 1, M I(x,y, i ) L(x,y, i ) i I AC (x,y) Scatter: Energy window subtraction 30000 Energy Spectrum of Sm-153 P(x,y) = projections w/ scatter P LE (x,y) = projection at lower energy P HE (x,y) = projection at higher energy P SC (x,y) = P(x,y) k L.P LE (x,y) k H.P HE (x,y) Counts 20000 10000 Lower Scatter Window Photo- Peak Window Upper Scatter Window STD in acrylic STD in air STD in acrylic with TEW Scatter Correction 0 25 50 75 100 125 150 Photon Energy [kev]

Outline Review of SPECT principles Iterative SPECT reconstruction Hybrid SPECT/CT imaging SPECT/CT quality assurance Commercial SPECT/CT systems SPECT/CT clinical applications

SPECT Iterative Reconstruction Maximum Likelihood-Expectation Maximization (ML-EM) Accounts for the statistical nature of SPECT imaging Incorporates the system response p(b,d) the probability that a photon emitted from an object voxel b is detected by projection pixel d p(b,d) captures 1. Depth-dependent resolution 2. Position-dependent scatter 3. Depth-dependent attenuation voxel b detector d Use a measured attenuation map along with models of scatter and camera resolution to perform a far more accurate reconstruction

SPECT Iterative Recon: Attenuation Modeling along a line integral g(s, ) = f(x,y) * p attn (x,y,s, ) p attn (x,y,s, ) = probability due to attenuation p attn (x,y,s, ) = exp(- ab (x,y ) x,y )) b a

SPECT Iterative Recon: System Resolution Modeling Distance-dependent collimator beam R s = R 2 i + R 2 c r Pencil Beam (FBP) Intrinsic Detector Resolution R i Fan Beam (2D - iterative) Cone Beam (3D iterative)

SPECT Iterative Recon: Resolution Modeling 2D: g(s, ) = f(x,y) * p res (x,y,s, ) 3D: g(s, ) = f(x,y,z) * p res (x,y,z,s, ) p res = probability due to resolution fan of acceptance (2D fan beam model) cone of acceptance (3D cone beam model)

SPECT Imaging: Scatter Scatter compensation occurs before attenuation the photopeak window contains scatter attenuation accounts for the removal of photopeak photons Scatter contribution estimated as a weighted sum of one or more adjacent energy window images, Ci(x,y, ) S(x,y, ) = i k i C i (x,y, ) Subtract scatter prior to reconstruction P corr (x,y, ) P(x,y, ) - S(x,y, ) Incorporate scatter into forward projection P(x,y, ) P corr (x,y, ) + S(x,y, ) SC techniques: DEW TEW ESSE

SPECT Iterative Reconstruction True projection intensity = sum of true voxel intensities weighted by detection probabilities Forward Projection B y( d) ( b) p( b, d) b 1 True voxel intensity = sum of true detector intensities weighted by detection probabilities Back Projection D ( b) y( d) p( b, d) d 1

Iterative Reconstruction Flow Diagram D [ k ] ( b) B d 1 [ k 1] b ' 1 ( b) D d 1 yd ( ) pbd (, ) [ k ] pbd (, ) ( b') p( b', d) In clinical practice, the stopping criteria is number of iterations (a time constraint) instead of a convergence criteria.

Ordered Subset EM (OSEM) Each OSEM iteration is a ML-EM iteration using an ordered subset of n (out of N) projections (eg: 4/36 views - 9 subsets, start with 0,90,180,270 views) The next OSEM iteration starts with the result of the previous OSEM iterations but uses a different ordered subset of n projections (next set uses 10,100,190,280 views) rate of convergence by using an ordered subset of all N projections for each iteration m OSEM iterations with n subsets each m n ML-EM iterations using all N each time

OSEM Iterative SPECT Reconstruction: Attenuation and Scatter Correction Un-Corrected Corrected Note the hot-rim artifact

OSEM Iterative SPECT Reconstruction: Collimator Resolution Modeling 99m Tc Bone Scan (osteosarcoma), LEHR Collimator Standard Filtered Backprojection 2-D OSEM w/ fan beam modeling (m=12,n=10) 2-D pre-filter: Butterworth, fc = 0.6 Nyquist, order = 10 3-D OSEM w/ cone beam modeling (m=25,n=10) 3-D Gaussian Post-Filter (7.8 mm FWHM)

Outline Review of SPECT principles Iterative SPECT reconstruction Hybrid SPECT/CT imaging SPECT/CT quality assurance Commercial SPECT/CT systems SPECT/CT clinical applications

SPECT/CT Hybrid Imaging: Why? Non-uniform attenuation maps required Previous methods used constant maps that work for brain but are problematic for thorax and pelvis radioactive source-based transmission CT time penalty Functional-anatomical overlay (image fusion) Improve localization of uptake regions Increase confidence in interpretation

CT-based AC for SPECT/CT CT CT noise reduced CT AC μ map Smooth, re bin CT to match SPECT Register CT w/ SPECT Apply bi linear transform on pixel by pixel basis Reconstructed SPECT Transition Matrix a ijk Other factors: SPECT projections Scatter estimates Collimator response

CT-based values 0.3 (cm 2 /g) 0.2 0.1 0 Material attenuation versus Energy Air Muscle Bone Photoelectric effect dominant CT 0 100 200 300 400 500 Energy (kev) Compton scatter dominant m = k CT-HU (simple but not accurate) Compton Scatter probability proportional to e - density Photoelectric effect probability proportional to (Z/E) 3 Attenuation mismatch between PE and CS with energy for high Z

CT-based values - HU-to-cm -1 conversion - not linearly related - piece-wise linear - bi- or tri-modal - Effective energy differences - CT (~ 70 80 kev) - SPECT (nuclide dependent) eg: 140 kev for Tc-99m 0.3 0.25 CT Number-to-Tc-99m value Function value (cm-1) 0.2 0.15 0.1 0.05 0-1000 0 200 CT Number (HU) 1000

SPECT/CT Hybrid Imaging: Iterative Reconstruction FBP w/ Butterworth 0.4/5 99m Tc EC-DG (NSCLC) 3-D OSEM w/ resolution modeling 3-D OSEM w/ resolution and attenuation modeling

Outline Review of SPECT principles Iterative SPECT reconstruction Hybrid SPECT/CT imaging SPECT/CT quality assurance Commercial SPECT/CT systems SPECT/CT clinical applications

SPECT/CT QA/QC Planar (AAPM Reports 6 and 9; NEMA NU 1-1994) Inherently includes all planar gamma camera QA Energy/Spatial resolution, uniformity, deadtime, sensitivity, rotational uniformity, opposed-head registration, etc. SPECT (AAPM Report 22 and 52) Uniformity and Contrast Resolution SPECT/CT (AAPM TG 177: Jim Halama) NM-CT registration CT-HU to linear attenuation ( ) transformation

NM-CT Registration Use Co-57 button sources w/ SPECT phantom

CT-HU to -map transformation Use an electron density phantom CIRS Inc. CT image: -790 to 235 HU

Outline Review of SPECT principles Iterative SPECT reconstruction Hybrid SPECT/CT imaging SPECT/CT quality assurance Commercial SPECT/CT systems SPECT/CT clinical applications

Commercial SPECT/CT systems Siemens SymbiaT (1-, 2-, 6, 16-slice CT) GE Hawkeye (1- or 4-slice CT) Philips BrightView (Flat-panel CT)

GE Millennium VG Hawkeye NM CT 3/8 and 1 NaI(Tl) crystals 16 simultaneous energy windows Slip-ring gantry Body-contouring based on infrared-based transmitters Co-planar, dental tube, 4-slice 20 mm beam no additional real estate needed Resolution: 3.5 or 1.75 mm (transaxial); 5 or 10 mm (axial) Time-averaged: 23 s per rotation (slow-scan) kvp: 120 140; ma: 1 2.5

Phillips BrightView XCT NM CT 3/8 and ¾ NaI(Tl) crystals Energy-independent flood calibration (up to 300 kev) 15 simultaneous energy windows Body-contouring based on tissue impedance Co-planar, flat-panel detector, 14 cm axial FOV no additional real estate needed High-resolution: 0.33 mm isotropic voxels Time-averaged: 12 s or 24 s per rotation (slow-scan) kvp: 120; ma: 5 80

NM CT Siemens - SymbiaT 3/8 and 5/8 NaI(Tl) crystals Energy-independent flood calibration (up to 300 kev) 6 simultaneous energy windows Body-contouring based on infrared-based transmitters Diagnostic CT scanner kvp: 80/110/130; ma: 20 345 (T16) & 30 240 (T6) Scan time: 0.5, 0.6, 1, 1,5 s per rotation 1-, 2-, 6-, and 16-slice CT scanners

Outline Review of SPECT principles Iterative SPECT reconstruction Hybrid SPECT/CT imaging SPECT/CT quality assurance Commercial SPECT/CT systems SPECT/CT clinical applications

Clinical SPECT/CT Imaging Stress/Rest Myocardial Perfusion Imaging Stress: 99m Tc-sestaMIBI or 99m Tc-Tetrafosmin Tetrafosmin Rest: 99m Tc-labeled agents or 201 Tl-chloride Tc-MDP: : bone diseases, bone metasteses Tc-sestaMIBI: : parathyroid adenomas Tc-sulphur colloid: : liver/spleen, lymphoscintigraphy In-Pentetreotide: neuroendocrine cancers In-ProstaScint: : prostate cancer 131 I-MIBG: pheochromocytoma, neuroblastoma 131 I-NaI: : thyroid cancer 99m Tc 99m Tc 99m Tc 111 In 111 In 123 I/ 131 131

Clinical SPECT/CT Imaging 99m Tc-CEA CEA: : colorectal cancer 99m Tc-RBCs RBCs: hemangioma 99m Tc-HMPAO HMPAO, -ECD:: brain perfusion 111 In-WBC WBC: : infection 67 Ga-citrate citrate: : inflammation, lymphoma 201 Tl-chloride chloride: : tumor perfusion

Clinical Benefits of SPECT/CT Visualization, diagnosis and interpretation of primary and metastatic diseases higher sensitivity and contrast than Planar imaging CT scan increases confidence in interpretation of SPECT examination Surgical planning and IMRT treatment planning 90 Y-microspheres radio-embolotherapy (selective internal RT or micro-brachytherapy) Internal radio-pharmaceutical therapy planning

SPECT/CT: Limitations Patient motion between SPECT and CT scans respiratory and cardiac motion during SPECT acquisitions Contrast CT contrast introduces electron density-material mismatch map algorithms do not yet account for contrast CT Absolute quantification (Bq/ml) not yet fully developed radionuclide-dependent acquisition/reconstruction technique-dependent calibration techniques not yet standardized

SPECT/CT: Future Applications Whole body SPECT/CT (analogous to PET/CT) Quantification of absolute activity (like PET) Compensation for CT contrast in map Compensation for respiratory, cardiac motion SPECT/CT-based 3-D dosimetry/treatment planning

Future: Whole-body Bone SPECT/CT Tc-99m MDP Bone Imaging S. Cheenu Kappadath, PhD AAPM 2009 - Anaheim, CA

99m-Tc MDP SPECT/CT: Fused Coronal views

Future: Multi-nuclide SPECT/CT Maximum Intensity Projection (MIP) of a dual-isotope (Tc-99m and I-123) SPECT/CT mouse study. Published by the Molecular Imaging Center for Excellence newsletter, SNM publication Volume 2, 2008