John D. Idoine

Coded Aperture Nuclear Scintigraphy: A Novel Small Animal Imaging Technique

We introduce and demonstrate the utility of coded aperture (CA) nuclear scintigraphy for imaging small animals. CA imaging uses multiple pinholes in a carefully designed mask pattern, mounted on a conventional gamma camera. System performance was assessed using point sources and phantoms, while several animal experiments were performed to test the usefulness of the imaging system in vivo, with commonly used radiopharmaceuticals. The sensitivity of the CA system for 99mTc was 4.2 x 10(3) cps/Bq (9400 cpm/microCi), compared to 4.4 x 10(4) cps/Bq (990 cpm/microCi) for a conventional collimator system. The system resolution was 1.7 mm, as compared to 4-6 mm for the conventional imaging system (using a high-sensitivity low-energy collimator). Animal imaging demonstrated artifact-free imaging with superior resolution and image quality compared to conventional collimator images in several mouse and rat models. We conclude that: (a) CA imaging is a useful nuclear imaging technique for small animal imaging. The advantage in signal-to-noise can be traded to achieve higher resolution, decreased dose or reduced imaging time. (b) CA imaging works best for images where activity is concentrated in small volumes; a low count outline may be better demonstrated using conventional collimator imaging. Thus, CA imaging should be viewed as a technique to complement rather than replace traditional nuclear imaging methods. (c) CA hardware and software can be readily adapted to existing gamma cameras, making their implementation a relatively inexpensive retrofit to most systems.

Improved optical sub-systems for intraoperative near-infrared fluorescence imaging

Near-infrared light propagation through living tissue provides promising opportunities for the development of non-invasive imaging techniques for human care. We have developed a Fluorescence-Assisted Resection and Exploration (FLARE) imaging system for surgery. The FLARE system uses invisible near-infrared light to help the surgeon visualize critical structures intraoperatively and in real-time. We present here the continued optimization of our imaging system from a research prototype to an efficient and ergonomic tool to be used during human surgery. New, hands-free operation enables the surgeon to zoom, focus, recall and save images through a footswitch. A LabVIEW curve-fitting algorithm, in combination with stepper motor control, provides auto-focus capability. Cardiac and/or respiratory gating minimizes motion artifacts of moving objects in the surgical field, and permits in-focus imaging during long fluorescence integration times. Automated subtraction of the near-infrared fluorescence signal from background reflections minimizes the effect of ambient illumination and improves the contrast to noise ratio with only moderate effects on intensity precision. Taken together, this study improves several optical components of the FLARE system, and helps ready it for human clinical testing.

Optimization of Coded Aperture Radioscintigraphy for Sentinel Lymph Node Mapping

PurposeRadioscintigraphic imaging during sentinel lymph node (SLN) mapping could potentially improve localization; however, parallel-hole collimators have certain limitations. In this study, we explored the use of coded aperture (CA) collimators.ProceduresEquations were derived for the six major dependent variables of CA collimators (i.e., masks) as a function of the ten major independent variables, and an optimized mask was fabricated. After validation, dual-modality CA and near-infrared (NIR) fluorescence SLN mapping were performed in pigs.ResultsMask optimization required the judicious balance of competing dependent variables, resulting in sensitivity of 0.35%, XY resolution of 2.0xa0mm, and Z resolution of 4.2xa0mm at an 11.5-cm field of view. The findings in pigs suggested that NIR fluorescence imaging and CA radioscintigraphy could be complementary, but present difficult technical challenges.ConclusionsThis study lays the foundation for using CA collimation for SLN mapping, and also exposes several problems that require further investigation.

Sub-Millimeter Technetium-99m Calibration Sources

PURPOSEnSmall animal radioscintigraphic imaging systems aim to achieve sub-millimeter resolution. At the present time, sub-millimeter calibration sources that can be placed at will within an imaged volume are not readily available. We have developed a method for producing technetium-99m (Tc-99m) sources in less than 15 minutes with readily available reagents.nnnPROCEDURESnTc-99m pertechnetate [TcO(4)](-) was incubated with 45 microm to 106 microm diameter spherical anion exchange beads, washed, and mounted as desired for instrument calibration.nnnRESULTSnThe procedure yields spherical sources having between 6.8 microCi to 11.1 microCi of Tc-99m per source. This work shows that dual imaging of these sources using white light and radioscintigraphy permits measurement of system performance with high precision.nnnCONCLUSIONnEasily prepared, sub-millimeter Tc-99m spherical calibration sources are described, and it is demonstrated that such sources are useful for measuring the resolution and sensitivity of radioscintigraphic systems, such as those designed for small animal imaging.

The product of normalized cerebral metabolic and cerebral flow reserve factors accounts for most variability in mild cognitive impairment and early dementia

Background: Cognitive impairment includes neurodegenerative and cerebrovasular components which are seldom isolated and usually coexist. Neurodegeneration is primarily characterized by metabolic markers such as fluorodeoxy-glucose (FDG). We reported direct relation between cerebrovascular disease, including stroke, and a brain SPECT derived cerebral flow reserve index (FRi). Here we report that the product of a scaled, normalized cerebral metabolic index (CMi) and FRi, both from brain SPECT, quantitatively measures cognitive impairment.

Corrected cerebral flow reserve as a marker of dementia risk

granular zone of the dentate gyrus of the hippocampus give rise to interneurons of the olfactory bulb and neurons of the granule cell layer of the dentate gyrus. Glycogen synthase kinase-3 beta (GSK-3beta) is a serine/threonine kinase originally identified as a regulator of glycogen metabolism but it also plays a pivotal role in numerous cellular functions. Considering the important role of GSK-3beta in neuroprotection and its role in regulating neuronal differentiation, we speculated that this enzyme could have a role in hippocampal stem/progenitor cells. Methods:We have used an in vitro approach using neurosphere cultures isolated from rat hippocampus to analyze the role of different GSK-3 beta inhibitors upon growth, migration of cells out of the neurospheres and differentiation towards a neuronal phenotype. We have also studied the effect of GSK-3 beta inhibition in in vivo neurogenesis by analyzing neuroblasts formation in the hippocampus of adult rats. Results: Our studies showed that inhibitors of GSK-3 beta are potent inducers of neuroblasts formation in the subgranularzone of the dentate gyrus of the hippocampus (one of the regions in which neurogenesis takes place in the adult brain) of adult rats. Also, in vitro studies demonstrate that inhibition of GSK-3 beta induces proliferation, migration, and differentiation of neural stem cells towards a neuronal phenotype.Conclusions:Our studies showed that inhibitors of GSK-3 beta are potent inducers of neuroblasts formation in the sub granular zone of the dentate gyrus of the hippocampus (one of the regions in which neurogenesis takes place in the adult brain) of adult rats. Also, in vitro studies demonstrate that inhibition of GSK-3 beta induces proliferation, migration, and differentiation of neural stem cells towards a neuronal phenotype.

Corrected Cerebral Flow Reserve from Brain SPECT as a Marker of Dementia Risk

Background: Mixed Dementia (including Alzheimer’s) risk may be increased by hypertension (BP), diabetes mellitus (DM), waist-height ratio (WH), traumatic brain injury (TI), thyroid (Td), renal (Rd), pituitary (Pd) disease and depression (De). To study dementia pathogenesis we developed a brain SPECT measure of cerebral flow reserve (CFi) with correction factors due to decreased tracer clearance in Rd.

P2-363: Omega-3 fat use to stimulate brain perfusion for early diagnosis of dementia and possible therapy

(defined here as CDR 0.5) and a CDR Sum-of-Boxes (CDR-SB) between 0.5 and 3.5 at the time of scanning (baseline). During scanning, subjects performed a visual scene-encoding paradigm (Dickerson BC et al., Ann Neurol 2004). fMRI data were analyzed (SPM2) using an ROI approach in which a mask was created of hippocampal clusters showing differential activation in the Novel vs. Repeated (NvR) contrast at the group level. Clusters were included in the mask if voxels within the cluster were significant at p .005 (uncorrected) and the cluster itself was significant at p .05 (small-volume correction). Hippocampal activation was quantified by extracting the SPM parameter estimate of NvR from this mask from each individual’s data. A linear regression model was created to predict degree of future cognitive decline (change in CDR-SB score after scanning) from baseline age, CDR-SB, and hippocampal activation. Partial correlations were run to examine the effect of each variable, controlling for the others. Results: The decline in CDR-SB after scanning ranged from 0 to 4.5 points (mean 1.88, S.D. 1.45). The linear regression model predicted cognitive decline (p .04), and partial correlation analyses revealed an effect of left hippocampal activation, controlling for the other predictors (r 0.53, p .006). Conclusions: These results suggest that fMRI may be a useful tool for predicting subsequent cognitive decline in individuals with MCI. Within a group of individuals with MCI spanning a range of mild impairment in daily life, greater hippocampal activation at the time of scanning predicted a greater degree of future cognitive decline.