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Bradley E Patt

Publications and source records attributed to Bradley E Patt.

4 recordsLinked to original sources

Intravascular radiation detectors for the detection of vulnerable atheroma.

An intravascular catheter was developed to identify inflammation in coronary atheroma. Inflammation in atheroma is associated with large numbers of macrophages. These cells have increased metabolism, increased expression of chemotactic receptors, and a high frequency of apoptosis-associated phosphatidylserine expression. Each of these parameters can be identified in vivo using specific radiolabeled agents: metabolism can be identified with 18F fluorodeoxyglucose (FDG), receptor expression with 99mTc monocyte chemotactic peptide-1, and apoptosis with 99mTc annexin V. The locally increased concentration of these tracers is readily demonstrable in experimental lesions by ex vivo autoradiography; however, the small lesion size makes it difficult to identify atheroma in the coronaries with conventional imaging equipment. In contrast, with a radiation-sensitive catheter, optimized to sense charged particle rather than gamma or x-radiation, specific lesions could be identified and localized. Charged particle radiation is emitted as a byproduct of nearly all radioactive decay but is typically most abundant in radionuclides that decay by beta emission (either positrons or negatrons). Prototype catheters, using a plastic scintillator mated to an optical fiber, have been tested in the laboratory with the positron-emitting radiopharmaceutical 18FDG. The catheter had sufficient sensitivity to detect lesions concentrating nanocurie concentrations of 18FDG. Ex vivo experiments in apo-e-/- mice confirmed the ability of the catheter to detect 18FDG in aortic lesions. These feasibility studies demonstrate the sensitivity of a beta-sensitive catheter system. Additional mechanical refinements are needed to optimize the system in anticipation of in vivo animal studies.

Animals↗

Rationale for the combination of nuclear medicine with magnetic resonance for pre-clinical imaging.

Multi-modality combinations of SPECT/CT and PET/CT have proven to be highly successful in the clinic and small animal SPECT/CT and PET/CT are becoming the norm in the research and drug development setting. However, the use of ionizing radiation from a high-resolution CT scanner is undesirable in any setting and particularly in small animal imaging (SAI), in laboratory experiments where it can result in radiation doses of sufficient magnitude that the experimental results can be influenced by the organism's response to radiation. The alternative use of magnetic resonance (MR) would offer a high-resolution, non-ionizing method for anatomical imaging of laboratory animals. MR brings considerably more than its 3D anatomical capability, especially regarding the imaging of laboratory animals. Dynamic MR imaging techniques can facilitate studies of perfusion, oxygenation, and diffusion amongst others. Further, MR spectroscopy can provide images that can be related to the concentration of endogenous molecules in vivo. MR imaging of injected contrast agents extends MR into the domain of molecular imaging. In combination with nuclear medicine (NM) SPECT and PET modalities in small animal imaging, MR would facilitate studies of dynamic processes such as biodistribution, pharmacokinetics, and pharmacodynamics. However, the detectors for nearly all PET and SPECT systems are still based on vacuum tube technology, namely: photomultiplier tubes (PMT's) in which the signal is generated by transporting electrons over a substantial distance within an evacuated glass tube, making them inoperable in even small magnetic fields. Thus the combination of SPECT or PET with MR has not been practical until the recent availability of semiconductor detectors such as silicon avalanche photodiodes (APD's) for PET and CdZnTe (CZT) detectors for SPECT coupled with the availability of high-density low noise ASIC electronics to read out the semiconductor detectors. The strong advantage of these technologies over PMT's is their insensitivity to magnetic fields which makes their use in co-axial multi-modality nuclear medicine/magnetic resonance instrumentation possible.

Animals↗

A novel silicon array designed for intraoperative charged particle imaging.

A novel Si-PIN imaging array is under investigation for a charged particle (beta, positron, or alpha) sensitive intraoperative camera to be used for (residual) tumor identification during surgery. This class of collimator-less nuclear imaging device has a higher signal response for direct interactions than its scintillator-optical detector-based counterparts. Monte Carlo simulations with 635 keV betas were performed, yielding maximum and projected ranges of 1.64 and 0.55 mm in Si. Up to 90% of these betas were completely absorbed in the first 0.30 mm. Based on these results, 300 microm thick prototype Si detector arrays were designed in a 16 x 16 crossed-grid arrangement with 0.8 mm wide orthogonal strips on 1.0 mm pitch. A NIM- and CAMAC-based high-density data acquisition and processing system was used to collect the list mode data. The system was calibrated by comparisons of measured spectra to energy deposition simulations or by direct measurement of various >100 keV conversion electron or beta emitters. Mean electronic noise per strip was <3.6 keV FWHM at room temperature. When detecting positrons, which have an accompanying 511 keV annihilation background, the flood irradiated beta/gamma ratio was approximately 40, indicating that beta images could be made without the use of background rejection techniques. The intrinsic spatial resolution corresponds to the 1 x 1 mm2 pixel size, and measurements of beta emitting point and line sources yielded FWHM resolutions of 1.5 (lateral) and 2.5 mm (diagonal), respectively, with the larger widths due to particle range blurting effects. Deconvolution of the finite source size yielded intrinsic resolutions that corresponded to the image pixel size. Transmission images of circle and line phantoms with various hole sizes and pitch were resolved with either pure beta or positron irradiation without a background correction. This novel semiconductor imaging device facilitates high charged particle and low gamma sensitivity, high signal/noise ratio, and allows for compact design to potentially aid surgical guidance by providing in situ images of clinical relevance.

Alpha Particles↗

Intravascular probe for detection of vulnerable plaque.

PURPOSE: Coronary angiography defines geometry of lumen of artery. However, perhaps 70% of heart attacks occur when minimally obstructive thin capped fibroatheroma rupture, causing thrombus and arterial occlusion. We have developed an intravascular imaging detector to identify vulnerable coronary artery plaque. PROCEDURE: Detector measures beta or conversion electron emissions from plaque-binding radiotracers. Detector assembly fits into a 2-mm diameter catheter and overcomes technical constraints of size, sensitivity, and conformance to intravascular environment. RESULTS: Device was tested by stepping test point sources past detector to verify function. System resolution is 6.7 mm and sensitivity is 400 cps/microCi one mm from detector. CONCLUSION: This prototype is a first step in imaging of labeled vulnerable plaque in coronary arteries. This type of system may assist in development of targeted and cost effective therapies to lower incidence of acute coronary artery diseases (CAD) such as unstable angina, acute myocardial infarction, and sudden cardiac death.

Beta Particles↗