Integrated PET/CT systems State of the art and Clinical Applications

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Integrated PET/CT systems State of the art and Clinical Applications V. Bettinardi Nuclear Medicine Dep. Scientific Institute San Raffaele Hospital Milan Italy

The announcement of a new Diagnostic Imaging System (Integrated PET/CT or Hybrid PET/CT system) has been reported in the Time Magazine as the Medical Invention of the year (2000) to go with the title of most outstanding basic science paper the team members received from the Journal of Nuclear Medicine

Why integrated PET/CT systems? 18 F-FDG The major success of PET in oncology is it s ability to detect tumours as increased levels of [ 18 F]-fluoro-2-deoxyglucose (FDG) uptake compared to normal tissues

Why integrated PET/C systems? The poor spatial resolution of a PET system (4-5mm) makes difficult the interpretation of PET images due to the lack of identifiable anatomical structures. Localization of increased tracer uptake to a specific organ or structure is important when decisions affecting the diagnosis, staging and the treatment of the patient have to be taken. The need for an accurrate anatomical localization of the PET signal was the motivation for the PET/CT systems.

Integrated PET/CT systems A PET/CT system combines (in the same gantry) two of the most important (and complementary ) diagnostic imaging systems like CT and PET allowing to perform the PET/CT procedure, in a single study session, without moving the patient from the bed CT PET

Integrated PET/CT systems The anatomical study : CT

Integrated PET/CT systems The functional study : Multiple bed positions PET

Integrated PET/CT systems The functional study : PET

Integrated PET/CT systems The functional study : PET

Integrated PET/CT systems The functional study : PET

Integrated PET/CT Systems In a PET/CT system both techniques use the same spatial reference system

Integrated PET/CT systems Once reconstructed, the CT and PET images are spatially co-registered, allowing the physicians to fuse both the information and thus to localize the PET signals over the corresponding anatomy / anatomical structure. Lymph node metastasis Bone metastasis HSR Milano

Integrated PET/CT systems CT images are also used for the Attenuation Correction of PET EM data CT based Attenuation Correction has significant advantages over more traditional methods (Measured Transmission AC - MAC ) : 1) Much lower statistical noise compared to MAC 2) Shorter acquisition time ( CT: 20-40sec Vs MAC: 20-30min) 3) Unbiased post injection CT scan PET Without AC CT PET With AC by CT

State of art of PET/CT systems Siemens mct General Electric (GE) Discovery-600 Discovery-690 Philips Gemini-GXL Gemini-TF An important characteristic of the PET/CT systems is to combine, in the same gantry, the state of the art of both technologies

Integrated PET/CT Helical Multi Slices CT scanners Helical CT scnner First models of PET/CT systems were equipped with : 2... 4. 1cm 2cm 4cm State of the art PET/CT system are equipped with : 6.. 8 10 16. 40 64.128.

MS-CT Position-sensitive detector (rotating) X-ray fan beam (rotating) + + Fast & UltraFast Ceramic Scintillator + Photodiodes X-ray source (rotating)

State of the art and future of MS-CT Dual Sources Energy Discriminating Detectors kvp Switching 80keV 80keV 140keV 140keV Detector 1 Detector 2 Dual energy CT offers a more specific tissue characterization : m(e) w (E) CT [HU] = ------------------- x 1000 w(e) 140 kvp image 80 kvp image Thorsten R.et al.n : Eur Radiol (2007) 17: 1510 1517

State of art of PET/CT systems Siemens mct GE Discovery-600 Discovery-690 Philips Gemini-GXL Gemini-TF PET Scanners

PET Scintillators BGO GSO LSO LYSO Density (g/cm 3 ) 7.1 6.7 7.4 7.1 Effective Z 74 59 66 60 1/ @ 511keV (mm) 11.2 15.0 12.3 12.6 Decay Time (ns) 300 65 40 41 Relative Light Output % (to 100 for NaI(Tl) 15 30 75 80 Energy Resolution % (@ kev) 10(511) 8.5(511) 10(511) 11(511) Wavelength (nm) 480 430 420 420 Index of Refraction 2.15 1.85 1.82 1.81 IDEAL CHARACTERISTICS high stopping power, to maximize the probability to stop the radiation good energy resolution, to reject scatter events good time resolution, for counting rate linearity, low random rate (PET), TOF to be inexpensive for mass production

PET Scintillators Conti Physica Medica 25;1-11, 2009

PET Detector Design General Electric PET detector block D-600 (BGO) matrix 8X6 4.7x6.3x30 mm 3 D-690 (LYSO) 4.2x6.3x25mm3 Siemens PET detector block mct (LSO) matrix 13x13 4x4x 20 mm 3 PMT 7 6 2 1 5 3 4 PHILIPS PIXELAR Detector panels optically coupled to continuous light guide G-GXL (GSO) 4 x 6 x 30 mm 3 G-TF (LYSO) 4 x 4 x 22 mm 3

Photo-Detectors PMT PS PMT APD and PS APD PMT APD SiPM Active area (mm2) 1-2000 cm 2 1-100 mm 2 1-100 mm 2 Gain 10 5-10 7 10 2 10 5-10 6 Quantum efficiency 25% 60-80% <40% Temperature coefficient <1%/ C 2-3%/ C 3-5%/ C Magnetic suceptibility Very high No (up to 9.4T) No (up to 15T) Si PM

NON TOF Time-of-Flight LSO & LYSO Use time-of-flight to localize source along line of flight. Time of flight information reduces noise in images. Variance reduction given by: 2D / c t. TOF 500 ps timing resolution 7.5 cm localization 500 ps timing resolution 5 x reduction in variance! Reconstruction without TOF information assume that all the possible locations of the annihilation site along the LOR are equally likely. TOF information can be used in the Reconstruction of the PET data to constraint the possible locations of the annihilation site along the LOR SNR GAIN SENSITIVITY GAIN SNR TOF 2 D D ------------ = ------- = ----- SNR c t x t psec x cm D=20 cm D=35 cm D=20 cm D=35 cm 50 0.75 5.2 6.8 26.7 46.7 300 4.5 2.1 2.8 4.4 7.8 500 7.5 1.6 2.2 2.7 4.7 650 9.75 1.4 1.9 2.1 3.6

TOF LESION PHANTOM (Diameter = 27 cm - Activity ratio Lesion / Background = 6:1 ) Non-TOF similar contrast and scan time TOF lower noise 60s 60s similar contrast and noise TOF shorter scan 60s 180s Slide courtesy Joel Karp,University of Pennsylvania

Extended Axial Field-Of-View PET/CT (mct) Standard Extended axial FOV Axial 16.2 cm 21.6 cm Starting from the standard configuration which consists in a 16.2 cm axial FOV scanner the user can order, as an option, the addition of one more ring of detectors extending the axial FOV up to 21.6cm The extension of the FOV results in an increase of the overall System Sesitivity of 77% The design of an extended axial FOV open the way to a modular design of the PET systems and represents the first step toward a very wide axial PET scanner.

Clinical Advantages of the Extended Axial Field-Of-View bed # Standard FOV: 5 15 min Extended FOV: 4 8 min Higher sensitivity => shorter imaging per bed (same dose, same counts) Higher sensitivity => lower dose (same acq. time, same counts) Higher sensitivity => higher SNR ( same dose, same acq. time)

PET/CT Clinical Applications Oncology (90%) Cardiology ( 5%) Neurology ( 5%)

Oncological Applications of PET/CT 18F-FDG WB-PET The primary clinical applications of PET/CT is oncology for: - staging, - restaging, - follow -up - monitoring the response to therapies.

Oncology PET/CT for Radiotherapy Applications The state of the art in the technology of the RT systems is the intensity modulated radiation therapy (IMRT), in which many small pencil beams are used, under computer control, to conform the irradiated volume to complex and irregular shape. IMRT allows the beams to be modulated to the required intentisy for delivering highly conformal doses of radiation to the targets, while sparing the adjacent normal tissue structures. IMRT allows the design of tailored hot-spots (which Tomotherapy Helical treatment delivery receives much higher local dose) tumour mass (Dose painting). within the overall PET/CT allows to improve the Target Volume Definition by using the: Anatomical CT images for the definitionof the Gross Tumor Volume ( GTV) Functional PET images for the definition of the Biological Tumor Volume (BTV) By combining GTV and BTV a more accurate TVD can be obtained Lung Simulation: Courtesy MD Anderson Huston

Tumour CT-based TT Lynphonodes Greater than 1cm CT TOMOTHERAPY TREATMENT PLAN CT-based TT HSR Milano

Tumour PET/CT-based TT Lynphonodes Greater than 1cm Tumour Lynphonodes No significant uptake of FDG CT PET/CT TOMOTHERAPY TREATMENT PLAN CT-based TT PET/CT-based TT HSR Milano

Oncology PET/CT for Radiotherapy Applications Respiratory gating PET/CT (4D PET/CT) Specific Patient s motion Information can be used for a more accurate TVD and to personalize the treatment planning by reducing the overall PTV, increasing the dose to the tumour while sparing healthy tissues.

PET/CT for Cardiological Applications The value of PET/CT in cardiac imaging has extended beyond the assessment of myocardial viability and perfusion. The combination of PET and CT allows a comprehensive anatomical and functional mapping / assessment of the Heart and has demonstrated its use in diagnosing and managing coronary artery disease. HSR-Milan

Cardiological Application of PET/CT With the state of the art of MSCT scanner it is possible to image coronary arteries (non-invasively), to obtain important clinical information on the presence, severity, and characteristics of Coronary arthery disease (CAD) including the visualization of luminal obstruction and atherosclerosis plaques. The negative predictive value of CT is very high. LAD D1 LCX Case SM This suggest that CTA combined with the complementary information by PET (e.g. perfusion imaging) is likely to offer added value for the CAD evaluation. RCA CTA Image courtesy : Turku PET Centre Turku PET Centre, Finland

Cardiological Application of PET/CT Case SM O 15 -water parametric PET/CT hybrid images MBF 3 ml/g/min MBF 4 ml/g/min MBF 2 ml/g/min CTA+ Adenosine stress perfusion Courtesy:Turku PET Centre, Finland

Neurological Application of PET/CT Dementias (e.g. Alzheimer s) Epilepsy Movement Disorded (e.g. Parkinson, Huntingtons) Oncology Cerebravascular disease Tumour Tumour 18F-FDG Normal Brain 18F-FDG Oncology 11C-Choline Oncology 18F-FESP D2 dopamine receptors Movement disorders Parkinson

Prospective and future of the Hybrid PET/CT systems Nowadays Hybrid PET/CT is certainly on the most important cancer imaging modality. CT scanner Dual Energy CT Multispectral imaging Fastest Temporal Resolution (assessment of time-dependent parameters) Increased Axial FOV ( to capture whole organs in a single rotation ) Dose Reduction Techiques PET scanner New crystal scintillator / detector material Smaller crystal / detectors to improve spatial resolution Fastest crystal scintillator / detectors for TOF New Detector Desgin from PMT to APD to SiPMT APD could be used also for DOI correction Extended Axial FOV Improve System Sensitivity Dose Reduction