Expand the probe idea functionality (above points) to larger imaging systems. First Applications, Probes, Isotopes

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Gamma Ray and Beta Ray Probes Larry MacDonald Imaging Research Laboratory University of Washington Radiology http://depts.washington.edu/nucmed/irl/ 23 Oct. 2007 Oct.

1 Gamma Ray and Beta Ray Probes Larry MacDonald Imaging Research Laboratory University of Washington Radiology 23 Oct Oct Gamma Ray and Beta Ray Probes Probe implies hand-held device provides positioning flexibility real-time response Most relevant arena for probes is the operating room OR compatible Expand the probe idea functionality (above points) to larger imaging systems Oct Properties of Gamma Rays and Beta Rays Gamma Rays massless photons travel potentially long distances in body penetration is exponential: N=N 0 e -µ(mat.,e)*x typical ~ cm-m penetration, no maximum difficult to collimate mono-energetic (allows energy discrimination) Beta Rays (e- & e+) massive charged particles undergo many interactions in body penetration between exp.&linear typical ~ mm penetration, max. exists easy to collimate continuous distribution of energies up to a maximum (does not allow energy discrimination) Oct Probe Application Requirements Procedure efficacy depends on measurement system consisting of Labeled compound extracted from blood into tumor/roi high tumor-to-background remain in tumor for a time consistent with surgery and T 1/2 Radioisotope chemical properties for stable label appropriate half-life (T 1/2 ) emission compatible with the detector and patient safety First Applications, Probes, Isotopes 1940 s First application: tumor localization pre- & intra-operative First probe: Geiger-Muller gas filled low sensitivity no energy resolution Available Tracers In principle any Nuc. Med. (γ) / PET (β+) agent β+ easy to collimate short range --> good localization confounding presence of 511 kev annihilation photons γ difficult to collimate Radiation detector efficient to radiation insensitive to background (or discrimination capability) good energy resolution (eliminate background and scatter) adequate collimation spatial resolution Oct First isotope used with probe: 32-P (β-) E max = 1.7 MeV --> ~ 7-8 mm range in tissue T 1/2 =14d --> dosimetry issues Oct Oct

Contemporary Applications, Probes, Isotopes Clinical Sentinel lymph nodes (SLN) replace complete axillary LN dissection with excision of selective SLN Scintillation and solid-state pencil detectors

Brain tumor margins - scint./solidstate/combo imaging probes - β+(pet) Arterial vulnerable plaque - imaging catheters - β+(pet) Oct.

Pathology of first downstream lymph nodes (Sentinel node(s)) is indicative of disease spread. Removal of only Sentinel node(s) avoids complications of complete node basin dissection.

---> HIGH CONTRAST at nodes; nci sensitivity Pre-operative imaging in Nuc. Med. with conventional camera is not universal. Non-imaging gamma probes are used to find nodes during surgery. Oct.

2 Contemporary Applications, Probes, Isotopes Clinical Sentinel lymph nodes (SLN) replace complete axillary LN dissection with excision of selective SLN Scintillation and solid-state pencil detectors non-imaging small point detectors 99m-Tc labeled colloids designed to flow through lymph systems - not biologically active Research Sentinel lymph nodes - add imaging capability, expand disease base Brain tumor margins - scint./solidstate/combo imaging probes - β+(pet) Arterial vulnerable plaque - imaging catheters - β+(pet) Oct SLN Procedure: Evaluate Spread of Cancer Applied to melanoma, breast cancer. Other cancers being investigated. Pathology of first downstream lymph nodes (Sentinel node(s)) is indicative of disease spread. Removal of only Sentinel node(s) avoids complications of complete node basin dissection. 99m-Tc labeled colloid injected near primary tumor drains through lymphatics. NO BACKGROUND, except injection site ~ 100X node act. ---> HIGH CONTRAST at nodes; nci sensitivity Pre-operative imaging in Nuc. Med. with conventional camera is not universal. Non-imaging gamma probes are used to find nodes during surgery. Oct SLN Detection Technical Issues and Protocol Variations Probe - all quite similar Tracer - colloid particle size Injection site - subdermal / peritumorial / intratumorial / subcutaneous Number of injections Injection volume and activity Massage injection site? Injection - detection timing Detection mode: blue dye / gamma probe / preoperative imaging Dynamic imaging / early imaging / early+late imaging Number of nodes to remove Pathology Requirements - H&E staining / IHC /Cytology Oct SLN Theoretical Basis Patients present with earlier stage of disease Lymph flow is orderly and predictable Tumor cells disseminate sequentially The sentinel node is the first node encountered by tumor cells Sentinel node status predicts distant basin status Basin involvement is less frequent Battelle Healthcare Products Neo2000 cadmium zinc telluride (CZT) semiconductor detector Carewise Medical Products, Inc. C-Trak scintillation crystal (?) Commercial SLN Probes Non-imaging Tyco healthcare Navigator GPS cadmium telluride (CdTe) semiconductor detector Important Operating Properties of Probes Sensitivity (counts/sec./inj. activity) detector material detector size (depth) radiation type (γ/β) and energy Spatial resolution (resolving small nearby nodes) detector size (width / diameter) collimator opening Energy resolution (reject scatter) detector type (scintillation / semiconductor) detector material Oct Oct Oct

SLN Probe Design SLN Probe Detector Materials SLN Probe Uses cable to console ergonomic handle NaI(Tl) / CsI(Na) / BGO (scintillation crystal) OR CdTe / CdZnTe (semiconductor) γ-ray shielding

3 SLN Probe Design SLN Probe Detector Materials SLN Probe Uses cable to console ergonomic handle NaI(Tl) / CsI(Na) / BGO (scintillation crystal) OR CdTe / CdZnTe (semiconductor) γ-ray shielding electronics PMT for scintillators low noise amps./buffers field of view, spatial resolution dependent on detector size and collimator geometry --- multiple collimators available Oct scintillation crystal e.g. NaI(Tl), BGO, CsI(Tl) Scintillation crystals Indirect detection method γ high voltage ~ 1000V visible light photosensor e.g. PMT, photodiode atomic excitations scintillation photons photosensor conversion (photoelectron ) current γ energy (photo)electron (atomic ionizations) Semiconductors Direct detection method electron-hole pairs current low voltage ~ 50V Oct γ semiconductor material e.g. Si, CdTe, CZT, Ge, HgI 2 SUPERIOR ENERGY RESOLUTION POSSIBLE! Current common clinical applications Melanoma Breast cancer Active research application areas (oncology) Colon Head and neck Cervical / Reproductive Lung Oct Intra-Operative Imaging of Sentinel Lymph Nodes Oct Introduce a compact high-resolution gamma camera into the operating room Goals: Reduce time of surgical procedures/node search. Increase confidence that all implicated nodes are removed. Identify nodes near injection site. Find additional hot nodes hidden by attenuation. Advantages: Display isotope distribution live-time in O.R. Rapidly assay secondary node basins. Faster learning curve. Reduce surgical incision size & morbidity due to node removal. Quantifiable measure of activity in nodes. Oct Hand-Held Gamma Camera The Hand-Held Camera can be used pre-operatively and intra-operatively Simultaneous image and audible count rate indicator 1 mm intrinsic spatial resolution 2 cm square intrinsic FOV Multiple collimators dictate a range of imaging parameters. Smart algorithms identify activity concentrations in low statistics distributions Oct

pre-or imaging varies None Passive NM participation Active NM participation Nuclear medicine in the OR requires logistical

Med. Dept. image showed one focus in axilla No Primary: Primary had been previously removed 58 sec. Pre-Prep OR image: Axilla.

12 mci) Extreme Color Scale Thresholding to Visualize Low Activity Nodes superior pre-incision Color Scale Threshold 100% (same

2007 JWCI 2002-11-11-1000 Quickly Survey Secondary Node Basins OR imaging before patient preparation (patient anesthetized) -

Pre-Prep OR image: Supraclavicular Color Scale Threshold 5% superior pre-incision Oct.

4 Image acq./ processing PC LumaGEM in the Operating Room Articulating arm LumaGEM ~ 1 m 2 footprint wheel base Protocols vary widely Degree of pre-or imaging varies None Passive NM participation Active NM participation Nuclear medicine in the OR requires logistical coordination between NM & Surgery Monitor on back of gamma cam. (not shown) displays images in View-Thru format. Oct Nuc. Med. Dept. image showed one focus in axilla No Primary: Primary had been previously removed 58 sec. Pre-Prep OR image: Axilla. ROI activity: 4.5 kbq (0.12 mci) Extreme Color Scale Thresholding to Visualize Low Activity Nodes superior pre-incision Color Scale Threshold 100% (same image) 0.4% Melanoma on RT ant. shoulder axilla node ROI Oct JWCI Quickly Survey Secondary Node Basins OR imaging before patient preparation (patient anesthetized) - Familiarizes physician with count rates, node location 62 sec. Pre-Prep OR image: Supraclavicular Color Scale Threshold 5% superior pre-incision Oct JWCI Time sequence nodes Post-Excision Findings reference point source #sec: Two nodes excised Re-image axilla 3 rd node axilla: post-incision, pre-excision axilla: post-excision of two hot nodes #sec: Oct JWCI Locate more hot nodes in less time Increases confidence Degree of pre-or imaging varies None Passive NM participation Active NM participation Expanding beyond melanoma/breast Cost/Benefit Ratio Summary Discussion Oct Research Beta Ray Probes Oct

Technique Agent preferentially taken up in unstable plaque Label agent with β emitter β Probe Catheter for Unstable Plaque Two

tracers - detect β+, reject 511 kev γ s - Both scintillation and semiconductor versions developed - Phoswich detects β+ and 511

allow pulse discrimination Not Phoswich independent det.

length Detectors: scintillators+fibers or silicon direct detection silicon detectors signal cables continuous (gamma

5 Technique Agent preferentially taken up in unstable plaque Label agent with β emitter β Probe Catheter for Unstable Plaque Two detector options: Imaging β Probe for Brain Tumor Margins - Aid removal of tumor margins in the brain - Use 18 F or other PET tracers - detect β+, reject 511 kev γ s - Both scintillation and semiconductor versions developed - Phoswich detects β+ and 511 kev γ in coincidence PHOSWICH: two scint. materials with distinct timing prop. allow pulse discrimination Not Phoswich independent det. Phoswich Phoswich Inject agent Insert detector catheter into artery Linear detector array locates labeled plaque along artery length Detectors: scintillators+fibers or silicon direct detection silicon detectors signal cables continuous (gamma camera-like) discrete (PET-like) Beta ray imaging (short range localization, no γ- ray collimation possible) Detector Identification Through Light Separation for Miniature Imaging Probe Janecek et. al, IEEE Trans. Nucl. Sci., Vol. 51(3), 2004 Oct Oct

A dual scintillator - dual silicon photodiode detector module for intraoperative gamma\beta probe and portable anti-compton spectrometer

$A dual scintillator - dual silicon photodiode detector module for intraoperative gamma\beta probe and portable anti-compton spectrometer$ University of Wollongong Research Online Faculty of Engineering - Papers (Archive) Faculty of Engineering and Information Sciences 2008 A dual scintillator - dual silicon photodiode detector module for