Abstinence following intermittent methylphenidate exposure dose-dependently modifies brain glucose metabolism in the rat brain.

Methylphenidate (MP) is a psychostimulant chronically prescribed for the treatment of attention deficit hyperactivity disorder (ADHD). Additionally, MP users may take breaks from using the medication during "drug holidays," which may include short-term or long-term breaks from medication. The present study utilized fluorodeoxyglucose (FDG) positron emission tomography (PET) to analyze the effects of chronic oral MP use and abstinence on brain glucose metabolism (BGluM) in rats at two different doses: high dose (HD) and low dose (LD). The schedule of treatment was 3 weeks on-treatment and 1 week off-treatment for a period of 13 weeks, followed by an abstinence period of 4 total weeks. Results showed that chronic MP treatment using this schedule did not lead to significant changes in BGluM when comparing the control to HD MP groups. However, significant activation in BGluM was observed after periods of abstinence between control and HD MP rats in the following brain regions: the trigeminal nucleus, reticular nucleus, inferior olive, lemniscus, mesencephalic reticular formation, inferior colliculus, and several areas of the cerebellum. These brain regions and functional brain circuit play a role in facial sensory function, the auditory pathway, organizing connections between the thalamus and cortex, motor learning, auditory function, control over eye movement, auditory information integration, and both motor and cognitive functions. These results, when considered with previous studies, indicate that MP schedule of use may have differing effects on BGluM. BGluM following long-term MP use was dependent on MP dose and schedule of use in rats. This study was conducted in non-ADHD model rats with the aim to establish an understanding of the effects of MP itself, especially given the growing chronic off-label and prescribed use of MP. Further studies are needed for analysis of the drug's effects on an ADHD model.

Alcohol binge drinking decreases brain glucose metabolism and functional connectivity in adolescent rats.

Alcohol misuse represents a serious health concern, especially during adolescence, with approximately 18% of high school students engaging in binge drinking. Despite widespread misuse of alcohol, its effects on how the brain functions is not fully understood. This study utilized a binge drinking model in adolescent rats to examine effects on brain function as measured by brain glucose metabolism (BGluM). Following an injection of [18 FDG] fluro-2-deoxy-D-glucose, rats had voluntary access to either water or various concentrations of ethanol to obtain the following targeted doses: water (no ethanol), low dose ethanol (0.29 ± 0.03 g/kg), moderate dose ethanol (0.98 ± 0.05), and high dose ethanol (2.19 ± 0.23 g/kg). Rats were subsequently scanned using positron emission tomography. All three doses of ethanol were found to decrease BGluM in the restrosplenial cortex, visual cortex, jaw region of the somatosensory cortex, and cerebellum. For both the LD and MD ethanol dose, decreased BGluM was seen in the superior colliculi. The MD ethanol dose also decreased BGluM in the subiculum, frontal association area, as well as the primary motor cortex. Lastly, the HD ethanol dose decreased BGluM in the hippocampus, thalamus, raphe nucleus, inferior colliculus, and the primary motor cortex. Similar decreases in the hippocampus were also seen in the LD group. Taken together, these results highlight the negative consequences of acute binge drinking on BGluM in many regions of the brain involved in sensory, motor, and cognitive processes. Future studies are needed to assess the long-term effects of alcohol binge drinking on brain function as well as its cessation.

Effects of collimator angle, couch angle, and starting phase on motion-tracking dynamic conformal arc therapy (4D DCAT).

PURPOSE: The aim of this study was to find an optimized configuration of collimator angle, couch angle, and starting tracking phase to improve the delivery performance in terms of MLC position errors, maximal MLC leaf speed, and total beam-on time of DCAT plans with motion tracking (4D DCAT). METHOD AND MATERIALS: Nontracking conformal arc plans were first created based on a single phase (maximal exhalation phase) of a respiratory motion phantom with a spherical target. An ideal model was used to simulate the target motion in superior-inferior (SI), anterior-posterior (AP), and left-right (LR) dimensions. The motion was decomposed to the MLC leaf position coordinates for motion compensation and generating 4D DCAT plans. The plans were studied with collimator angle ranged from 0° to 90°; couch angle ranged from 350°(-10°) to 10°; and starting tracking phases at maximal inhalation (θ=π/2) and exhalation (θ=0) phases. Plan performance score (PPS) evaluates the plan complexity including the variability in MLC leaf positions, degree of irregularity in field shape and area. PPS ranges from 0 to 1, where low PPS indicates a plan with high complexity. The 4D DCAT plans with the maximal and the minimal PPS were selected and delivered on a Varian TrueBeam linear accelerator. Gafchromic-EBT3 dosimetry films were used to measure the dose delivered to the target in the phantom. Gamma analysis for film measurements with 90% passing rate threshold using 3%/3 mm criteria and trajectory log files were analyzed for plan delivery accuracy evaluation. RESULTS: The maximal PPS of all the plans was 0.554, achieved with collimator angle at 87°, couch angle at 350°, and starting phase at maximal inhalation (θ=π/2). The maximal MLC leaf speed, MLC leaf errors, total leaf travel distance, and beam-on time were 20 mm/s, 0.39 ± 0.16 mm, 1385 cm, and 157 s, respectively. The starting phase, whether at maximal inhalation or exhalation had a relatively small contribution to PPS (0.01 ± 0.05). CONCLUSIONS: By selecting collimator angle, couch angle, and starting tracking phase, 4D DCAT plans with the maximal PPS demonstrated less MLC leaf position errors, lower maximal MLC leaf speed, and shorter beam-on time which improved the performance of 4D motion-tracking DCAT delivery.

Effect of chirality on cellular uptake, imaging and photodynamic therapy of photosensitizers derived from chlorophyll-a.

We have previously shown that the (124)I-analog of methyl 3-(1'-m-iodobenzyloxy) ethyl-3-devinyl-pyropheophorbide-a derived as racemic mixture from chlorophyll-a can be used for PET (positron emission tomography)-imaging in animal tumor models. On the other hand, as a non-radioactive analog, it showed excellent fluorescence and photodynamic therapy (PDT) efficacy. Thus, a single agent in a mixture of radioactive ((124)I-) and non-radioactive ((127)I) material can be used for both dual-imaging and PDT of cancer. Before advancing to Phase I human clinical trials, we evaluated the activity of the individual isomers as well as the impact of a chiral center at position-3(1) in directing in vitro/in vivo cellular uptake, intracellular localization, epithelial tumor cell-specific retention, fluorescence/PET imaging, and photosensitizing ability. The results indicate that both isomers (racemates), either as methyl ester or carboxylic acid, were equally effective. However, the methyl ester analogs, due to subcellular deposition into vesicular structures, were preferentially retained. All derivatives containing carboxylic acid at the position-17(2) were noted to be substrate for the ABCG2 (a member of the ATP binding cassette transporters) protein explaining their low retention in lung tumor cells expressing this transporter. The compounds in which the chirality at position-3 has been substituted by a non-chiral functionality showed reduced cellular uptake, retention and lower PDT efficacy in mice bearing murine Colon26 tumors.

Exercise Influences the Brain's Metabolic Response to Chronic Cocaine Exposure in Male Rats.

Cocaine use is associated with negative health outcomes: cocaine use disorders, speedballing, and overdose deaths. Currently, treatments for cocaine use disorders and overdose are non-existent when compared to opioid use disorders, and current standard cocaine use disorder treatments have high dropout and recidivism rates. Physical exercise has been shown to attenuate addiction behavior as well as modulate brain activity. This study examined the differential effects of chronic cocaine use between exercised and sedentary rats. The effects of exercise on brain glucose metabolism (BGluM) following chronic cocaine exposure were assessed using Positron Emission Tomography (PET) and [18F]-Fluorodeoxyglucose (FDG). Compared to sedentary animals, exercise decreased metabolism in the SIBF primary somatosensory cortex. Activation occurred in the amygdalopiriform and piriform cortex, trigeminothalamic tract, rhinal and perirhinal cortex, and visual cortex. BGluM changes may help ameliorate various aspects of cocaine abuse and reinstatement. Further investigation is needed into the underlying neuronal circuits involved in BGluM changes and their association with addiction behaviors.

Characterization and Assessment of Projection Probability Density Function and Enhanced Sampling in Self-Collimation SPECT.

We have recently reported a self-collimation SPECT (SC-SPECT) design concept that constructs sensitive detectors in a multi-ring interspaced mosaic architecture to simultaneously improve system spatial resolution and sensitivity. In this work, through numerical and Monte-Carlo simulation studies, we investigate this new design concept by analyzing its projection probability density functions (PPDF) and the effects of enhanced sampling, i.e. having rotational and translational object movements during imaging. We first quantitatively characterize PPDFs by their widths and edge slopes. Then we compare the PPDFs of an SC-SPECT and a series of multiple-pinhole SPECT (MPH-SPECT) systems and assess the impact of PPDFs - combined with enhanced sampling - on image contrast recovery coefficient and variance through phantom studies. We show the PPDFs of SC- SPECT have steeper edges and a wider range of width, and these attributes enable SC-SPECT to achieve better performance.

Exercise Modifies the Brain Metabolic Response to Chronic Cocaine Exposure Inhibiting the Stria Terminalis.

It is well known that exercise promotes health and wellness, both mentally and physiologically. It has been shown to play a protective role in many diseases, including cardiovascular, neurological, and psychiatric diseases. The present study examined the effects of aerobic exercise on brain glucose metabolic activity in response to chronic cocaine exposure in female Lewis rats. Rats were divided into exercise and sedentary groups. Exercised rats underwent treadmill running for six weeks and were compared to the sedentary rats. Using positron emission tomography (PET) and [18F]-Fluorodeoxyglucose (FDG), metabolic changes in distinct brain regions were observed when comparing cocaine-exposed exercised rats to cocaine-exposed sedentary rats. This included activation of the secondary visual cortex and inhibition in the cerebellum, stria terminalis, thalamus, caudate putamen, and primary somatosensory cortex. The functional network of this brain circuit is involved in sensory processing, fear and stress responses, reward/addiction, and movement. These results show that chronic exercise can alter the brain metabolic response to cocaine treatment in regions associated with emotion, behavior, and the brain reward cascade. This supports previous findings of the potential for aerobic exercise to alter the brain's response to drugs of abuse, providing targets for future investigation. These results can provide insights into the fields of exercise neuroscience, psychiatry, and addiction research.

Unpredictable chronic mild stress differentially impacts resting brain glucose metabolism in fatty acid-binding protein 7 deficient mice.

Fatty acid-binding proteins (FABPs) are intracellular chaperone proteins involved in the trafficking of n-3 polyunsaturated fatty acids and endocannabinoids. Inhibiting two of the main FABP subtypes found in the brain (FABP5 and FABP7) hinders endocannabinoid uptake and hydrolysis. Prior data indicates that cannabinoid receptor stimulation can ameliorate the consequences associated with chronic stress. To this end, FABP expression may play a similar role in response to stressful conditions. Male C57BL/6 J (WT) and FABP7 knockout (KO) mice were assigned to either a non-stress cohort or an unpredictable chronic mild stress (UCMS) cohort for a period of 4 weeks. Immediately after 4 weeks, mice were injected with [18F]2-fluoro-2-deoxy-d-glucose (FDG) and scanned using micro positron emission tomography (mPET) to examine brain glucose metabolism (BGluM). WT mice exposed to UCMS showed reduced BGluM in striatal, cortical, and hypothalamic regions and showed increased BGluM in the hippocampus, thalamus, periaqueductal gray, superior colliculi, inferior colliculi, and cerebellum. In contrast, there were limited effects of UCMS on BGluM in FABP7 KO mice, with a reduction in the thalamus, periaqueductal gray, and superior colliculi. These findings provide novel insight into FABP7 expression and indicate this gene to play an important role in response to aversive stimuli.

Chronic treatment and abstinence from methylphenidate exposure dose-dependently changes glucose metabolism in the rat brain.

Methylphenidate (MP) is extensively prescribed for attention deficit hyperactivity disorder (ADHD). While MP is effective in ameliorating symptoms of ADHD, MP is also used illicitly among healthy subjects without ADHD for cognitive-enhancing purposes. The deleterious consequences associated with long-term MP use as well as its cessation on brain activity remains to be understood. To address this, we administered either water, low dose MP (LD MP), or high dose MP (HD MP) to healthy adolescent Sprague Dawley rats, with five days on the treatment and two days off for thirteen consecutive weeks. Rats were then abstinent from their respective treatments for four weeks. Using positron emission tomography (PET) and fluorodeoxyglucose [18F] (FDG), we scanned rats at three time points: after thirteen weeks of treatment, after one week of abstinence, and after four weeks of abstinence. After thirteen weeks of LD and HD MP treatment, increases in brain glucose metabolism (BGluM) were seen in several cortical and subcortical regions associated with sensory and motor functions as well as learning and memory. One-week abstinence from LD MP treatment promoted increased BGluM compared to both water treated and HP MP treated groups. After four weeks of abstinence, little group differences were seen. Longitudinally, we observed contrasting differences on BGluM depending on whether a LD or HD of MP was administered. Our results demonstrate that MP treatment during adolescence can significantly alter BGluM. Moreover, these changes in brain activity do not subside in many areas of the brain after both one and four-week drug abstinence.

A 3-dimensional stationary cascade gamma-ray coincidence imager.

Objective.For certain radionuclides that decay through emitting two or more gamma photons consecutively within a short time interval-called cascade gamma-rays, the location where a radiopharmaceutical molecule emits cascade gamma-rays can be identified through coincidence detection of the photons. If each cascade photon is detected through a collimation mechanism, the location of the molecule can be inferred from the intersection of the back-projections of the two photons.Approach.In this work, we report the design and evaluation of a three-dimensional stationary imager based on this concept for imaging distributions of cascade-emitting radionuclides in radiopharmaceutical therapy. The imager was composed of two gamma-ray cameras assembled in an L-shape. Both cameras were NaI(Tl) scintillator based, one with a multi-slit collimator, the other with a multi-pinhole collimator. The field of view (FOV) was 100 mm (∅) × 100 mm (L). Based on the unique characteristics of the cascade coincidence events, we used a direct back-projection algorithm to reconstruct point source images for assessing the imager's intrinsic spatial resolution and the standard maximum likelihood expectation maximization algorithm for reconstructing phantom images.Main results.We evaluated the performance of the imager in both simulated and prototype form with radionuclide177Lu (cascade photon emitter). On the simulated imager, the coincidence detection efficiency at the center of FOV was 3.85 × 10-6, the spatial resolution was 7.0 mm. On the prototype imager, the corresponding values were 3.20 × 10-6and 6.7 mm, respectively. Simulated hot-rod and experimental cardiac phantom studies demonstrate the first three-dimensional cascade gamma coincidence imager is fully functional.

Self-Collimating SPECT With Multi-Layer Interspaced Mosaic Detectors.

Conventional single photon emission computed tomography (SPECT) relies on mechanical collimation whose resolution and sensitivity are interdependent, the best performance a SPECT system can attain is only a compromise of these two equally desired properties. To simultaneously achieve high resolution and sensitivity, we propose to use sensitive detectors constructed in a multi-layer in ter spaced mosaicdetectors (MATRICES) architecture to accomplish part of the collimation needed. We name this new approach self-collimation. We evaluate three self-collimating SPECT systems and report their imaging performance: 1) A simulated human brain SPECT achieves 3.88% sensitivity, it clearly resolves 0.5-mm and 1.0-mm hot-rod patterns at noise-free and realistic count-levels, respectively; 2) a simulated mouse SPECT achieves 1.25% sensitivity, it clearly resolves 50- [Formula: see text] and 100- [Formula: see text] hot-rod patterns at noise-free and realistic count-levels, respectively; 3) a SPECT prototype achieves 0.14% sensitivity and clearly separates 0.3-mm-diameter point sources of which the center-to-center neighbor distance is also 0.3 mm. Simulated contrast phantom studies show excellent resolution and signal-to-noise performance. The unprecedented system performance demonstrated by these 3 SPECT scanners is a clear manifestation of the superiority of the self-collimating approach over conventional mechanical collimation. It represents a potential paradigm shift in SPECT technology development.

Highlights on the imaging (nuclear/fluorescence) and phototherapeutic potential of a tri-functional chlorophyll-a analog with no significant toxicity in mice and rats.

Herein we report the positron emission tomography (PET) imaging potential of a 124I-labeled radiopharmaceutical (PET-ONCO). In tumored mice, it shows high uptake in a variety of tumors: brain (GL261, U87), Colon (Colon26), lung (Lewis lung), breast (4 T1), bladder (UMUC3), pancreas (PANC-1) implanted in mice. This agent also shows promise for imaging associated metastatic disease (breast to lung, to bone). Interestingly, the iodinated compound derived from chlorophyll-a, in combination with the corresponding 124I-analog, can serve as a dual imaging agent (PET/fluorescence, complimentary to each other), with an option of photodynamic therapy (PDT). In contrast to Fluorine-18 (half-life 110 min), the Iodine-124 radionuclide has a physical half-life of roughly 4 days. Thus, unlike 18F-FDG, PET-ONCO can be transported longer distances. While the time for optimal tumor-uptake was observed at 24 h, improved tumor contrasts of both primary and metastasis were obtained at 48 and 72 h post- injection (i. v.) of PET-ONCO. In both mice and rats at a single dose study, PET-ONCO did not show any organ toxicity.

Compared to purpurinimides, the pyropheophorbide containing an iodobenzyl group showed enhanced PDT efficacy and tumor imaging (124I-PET) ability.

Two positional isomers of purpurinimide, 3-[1'-(3-iodobenzyloxyethyl)] purpurin-18-N-hexylimide methyl ester 4, in which the iodobenzyl group is present at the top half of the molecule (position-3), and a 3-(1'-hexyloxyethy)purpurin-18-N-(3-iodo-benzylimide)] methyl ester 5, where the iodobenzyl group is introduced at the bottom half (N-substitued cyclicimide) of the molecule, were derived from chlorophyll-a. The tumor uptake and phototherapeutic abilities of these isomers were compared with the pyropheophorbide analogue 1 (lead compound). These compounds were then converted into the corresponding 124I-labeled PET imaging agents with specific activity >1 Ci/micromol. Among the positional isomers 4 and 5, purpurinimide 5 showed enhanced imaging and therapeutic potential. However, the lead compound 1 derived from pyropheophorbide-a exhibited the best PET imaging and PDT efficacy. For investigating the overall lipophilicity of the molecule, the 3-O-hexyl ether group present at position-3 of purpurinimide 5 was replaced with a methyl ether substituent, and the resulting product 10 showed improved tumor uptake, but due to its significantly higher uptake in the liver, spleen, and other organs, a poor tumor contrast in whole-body tumor imaging was observed.

A Pyropheophorbide Analogue Containing a Fused Methoxy Cyclohexenone Ring System Shows Promising Cancer-Imaging Ability.

Herein we report the synthesis, photophysical properties, positron emission tomography (PET) imaging and photodynamic therapy (PDT) efficacy of methyl 3-(1'-m-iodobenzyloxy)ethyl-3-devinyl-verdin 4 (with or without the 124 I isotope). The PET imaging ability and ex vivo biodistribution of [124 I]4 were compared with the well-studied methyl [3-(124 1'-m-iodobenzyloxy)ethyl]-3-devinyl-pyropheophorbide-a methyl ester (PET-ONCO or [124 I]2) and [18 F]fluorodeoxyglucose ([18 F]FDG) in BALB/c mice bearing colon-26 tumors. Whole-body PET images of [124 I]4 containing a fused methoxy cyclohexenone ring system showed excellent tumor contrast with time (72>48>24 h post-injection). Ex vivo biodistribution results indicate that relative to the current clinical standard [18 F]FDG and [124 I]2 in 2 % ethanol formulation, [124 I]4, at the same radioactive dose (25 µCi per mouse), showed higher tumor uptake at 24 h post-injection and longer tumor retention. In biological environments, compound 4 showed lower fluorescence and lower singlet oxygen yield than 2, which is possibly due to higher aggregation caused by the presence of a fused cyclohexenone ring system, resulting in limited in vitro/in vivo PDT efficacy. Therefore, the chlorophyll-a analogue [124 I]4 provides easy access to a novel PET imaging agent (with no skin phototoxicity) to image cancer types-brain, renal carcinomas, pancreas-in which [18 F]FDG shows limitations.

Epidermal Growth Factor Receptor-Targeted Multifunctional Photosensitizers for Bladder Cancer Imaging and Photodynamic Therapy.

The in vitro and in vivo anticancer activity of iodinated photosensitizers (PSs) with and without an erlotinib moiety was investigated in UMUC3 [epidermal growth factor (EGFR)-positive] and T24 (EGFR-low) cell lines and tumored mice. Both the erlotinib-conjugated PSs 3 and 5 showed EGFR target specificity, but the position-3 erlotinib-PS conjugate 3 demonstrated lower photodynamic therapy efficacy than the corresponding non-erlotinib analogue 1, whereas the conjugate 5 containing an erlotinib moiety at position-17 of the PS showed higher tumor uptake and long-term tumor cure (severe combined immunodeficient mice bearing UMUC3 tumors). PS-erlotinib conjugates in the absence of light were ineffective in vitro and in vivo, but robust apoptotic and necrotic cell death was observed in bladder cancer cells after exposing them to a laser light at 665 nm. In contrast to 18F-fluorodeoxyglucose, a positron emission tomography agent, the position-17 erlotinib conjugate (124I-analogue 6) showed enhanced UMUC3 tumor contrast even at a low imaging dose of 15 µCi/mouse.

A novel method to calibrate DOI function of a PET detector with a dual-ended-scintillator readout.

The detection of depth-of-interaction (DOI) is a critical detector capability to improve the PET spatial resolution uniformity across the field-of-view and will significantly enhance, in particular, small bore system performance for brain, breast, and small animal imaging. One promising technique of DOI detection is to use dual-ended-scintillator readout that uses two photon sensors to detect scintillation light from both ends of a scintillator array and estimate DOI based on the ratio of signals (similar to Anger logic). This approach needs a careful DOI function calibration to establish accurate relationship between DOI and signal ratios, and to recalibrate if the detection condition is shifted due to the drift of sensor gain, bias variations, or degraded optical coupling, etc. However, the current calibration method that uses coincident events to locate interaction positions inside a single scintillator crystal has severe drawbacks, such as complicated setup, long and repetitive measurements, and being prone to errors from various possible misalignments among the source and detector components. This method is also not practically suitable to calibrate multiple DOI functions of a crystal array. To solve these problems, a new method has been developed that requires only a uniform flood source to irradiate a crystal array without the need to locate the interaction positions, and calculates DOI functions based solely on the uniform probability distribution of interactions over DOI positions without knowledge or assumption of detector responses. Simulation and experiment have been studied to validate the new method, and the results show that the new method, with a simple setup and one single measurement, can provide consistent and accurate DOI functions for the entire array of multiple scintillator crystals. This will enable an accurate, simple, and practical DOI function calibration for the PET detectors based on the design of dual-ended-scintillator readout. In addition, the new method can be generally applied to calibrating other types of detectors that use the similar dual-ended readout to acquire the radiation interaction position.

Lutetium oxyorthosilicate (LSO) intrinsic activity correction and minimal detectable target activity study for SPECT imaging with a LSO-based animal PET scanner.

This work is part of a feasibility study to develop SPECT imaging capability on a lutetium oxyorthosilicate (LSO) based animal PET system. The SPECT acquisition was enabled by inserting a collimator assembly inside the detector ring and acquiring data in singles mode. The same LSO detectors were used for both PET and SPECT imaging. The intrinsic radioactivity of (176)Lu in the LSO crystals, however, contaminates the SPECT data, and can generate image artifacts and introduce quantification error. The objectives of this study were to evaluate the effectiveness of a LSO background subtraction method, and to estimate the minimal detectable target activity (MDTA) of image object for SPECT imaging. For LSO background correction, the LSO contribution in an image study was estimated based on a pre-measured long LSO background scan and subtracted prior to the image reconstruction. The MDTA was estimated in two ways. The empirical MDTA (eMDTA) was estimated from screening the tomographic images at different activity levels. The calculated MDTA (cMDTA) was estimated from using a formula based on applying a modified Currie equation on an average projection dataset. Two simulated and two experimental phantoms with different object activity distributions and levels were used in this study. The results showed that LSO background adds concentric ring artifacts to the reconstructed image, and the simple subtraction method can effectively remove these artifacts-the effect of the correction was more visible when the object activity level was near or above the eMDTA. For the four phantoms studied, the cMDTA was consistently about five times of the corresponding eMDTA. In summary, we implemented a simple LSO background subtraction method and demonstrated its effectiveness. The projection-based calculation formula yielded MDTA results that closely correlate with that obtained empirically and may have predicative value for imaging applications.

Choice of crystal surface finishing for a dual-ended readout depth-of-interaction (DOI) detector.

The objective of this study was to choose the crystal surface finishing for a dual-ended readout (DER) DOI detector. Through Monte Carlo simulations and experimental studies, we evaluated 4 crystal surface finishing options as combinations of crystal surface polishing (diffuse or specular) and reflector (diffuse or specular) options on a DER detector. We also tested one linear and one logarithm DOI calculation algorithm. The figures of merit used were DOI resolution, DOI positioning error, and energy resolution. Both the simulation and experimental results show that (1) choosing a diffuse type in either surface polishing or reflector would improve DOI resolution but degrade energy resolution; (2) crystal surface finishing with a diffuse polishing combined with a specular reflector appears a favorable candidate with a good balance of DOI and energy resolution; and (3) the linear and logarithm DOI calculation algorithms show overall comparable DOI error, and the linear algorithm was better for photon interactions near the ends of the crystal while the logarithm algorithm was better near the center. These results provide useful guidance in DER DOI detector design in choosing the crystal surface finishing and DOI calculation methods.

Multipinhole SPECT helical scan parameters and imaging volume.

PURPOSE: The authors developed SPECT imaging capability on an animal PET scanner using a multiple-pinhole collimator and step-and-shoot helical data acquisition protocols. The objective of this work was to determine the preferred helical scan parameters, i.e., the angular and axial step sizes, and the imaging volume, that provide optimal imaging performance. METHODS: The authors studied nine helical scan protocols formed by permuting three rotational and three axial step sizes. These step sizes were chosen around the reference values analytically calculated from the estimated spatial resolution of the SPECT system and the Nyquist sampling theorem. The nine helical protocols were evaluated by two figures-of-merit: the sampling completeness percentage (SCP) and the root-mean-square (RMS) resolution. SCP was an analytically calculated numerical index based on projection sampling. RMS resolution was derived from the reconstructed images of a sphere-grid phantom. RESULTS: The RMS resolution results show that (1) the start and end pinhole planes of the helical scheme determine the axial extent of the effective field of view (EFOV), and (2) the diameter of the transverse EFOV is adequately calculated from the geometry of the pinhole opening, since the peripheral region beyond EFOV would introduce projection multiplexing and consequent effects. The RMS resolution results of the nine helical scan schemes show optimal resolution is achieved when the axial step size is the half, and the angular step size is about twice the corresponding values derived from the Nyquist theorem. The SCP results agree in general with that of RMS resolution but are less critical in assessing the effects of helical parameters and EFOV. CONCLUSIONS: The authors quantitatively validated the effective FOV of multiple pinhole helical scan protocols and proposed a simple method to calculate optimal helical scan parameters.

Polyacrylamide-based biocompatible Nanoplatform enhances the tumor uptake, PET/fluorescence imaging and anticancer activity of a chlorophyll analog.

In this report we demonstrate the outstanding advantages of multifunctional nanoplatforms for cancer-imaging and therapy. The non-toxic polyacrylamide (PAA) nanoparticles (size:18-25 nm) formulation drastically changed the pharmacokinetic profile of the ¹²4I- labeled chlorophyll-a derivative (formulated in 10% ethanol in PBS) with a remarkable enhancement in tumor uptake, and significantly reduced uptake in spleen and liver. Among the various nanoformulations investigated, the ¹²4I- labeled photosensitizer (dose: 0.6142 MBq), and the cyanine dye-nanoparticles (CD-NP) conjugate (dose 0.3 µmol/kg) in combination showed great potential for tumor imaging (PET/NIR fluorescence) in BALB/c mice bearing Colon26 tumors. Compared to free non-labeled photosensitizer, the corresponding PAA nanoformulation under similar treatment parameters showed a remarkable enhancement in long-term tumor cure by PDT (photodynamic therapy) and provides an opportunity to develop a single nanoplatform for tumor-imaging (PET/fluorescence) and phototherapy, a practical "See and Treat" approach.