The Nutritional Burden of Cancer: Nutritional Status and Body Composition Differences Between Children with Acute Lymphoblastic Leukemia and their Siblings in Guatemala.

During treatment, children with acute lymphoblastic leukemia (ALL) gain fat mass and lose skeletal muscle mass. The great majority live in low- and middle-income countries with few studies of their body composition and none addressing the hypothesis that the disease itself contributes to nutritional morbidity. At diagnosis, children with ALL were compared to their siblings on socioeconomic status (SES). Nutritional status was assessed by mid-upper arm circumference (MUAC)-for-age Z scores and body composition by dual energy x-ray absorptiometry (DXA). Median SES scores for the patients (47.5) and their siblings (47.0) were very similar (P = 0.5). MUAC Z scores for patients aged >5 years were lower than for siblings (P < 0.001). On DXA siblings had a higher mean appendicular lean mass index Z score, a surrogate of skeletal muscle mass, than patients (P = 0.019). A logistic model to estimate the odds ratio (OR) of being severely/moderately under-nourished (classified by MUAC Z score) by SES revealed that, compared with siblings (n = 49), children with ALL (n = 60) had a higher probability of being under-nourished (OR 5.25, 95% CI 1.44-25.95, P = 0.02). The results support the hypothesis that children at diagnosis of ALL in Guatemala are more nutritionally depleted than their apparently healthy siblings.

Comparison of ventilation defects quantified by Technegas SPECT and hyperpolarized 129Xe MRI.

Introduction: The ideal contrast agents for ventilation SPECT and MRI are Technegas and 129Xe gas, respectively. Despite increasing interest in the clinical utility of ventilation imaging, these modalities have not been directly compared. Therefore, our objective was to compare the ventilation defect percent (VDP) assessed by Technegas SPECT and hyperpolarized 129Xe MRI in patients scheduled to undergo lung cancer resection with and without pre-existing obstructive lung disease. Methods: Forty-one adults scheduled to undergo lung cancer resection performed same-day Technegas SPECT, hyperpolarized 129Xe MRI, spirometry, and diffusing capacity of the lung for carbon monoxide (DLCO). Ventilation abnormalities were quantified as the VDP using two different methods: adaptive thresholding (VDPT) and k-means clustering (VDPK). Correlation and agreement between VDP quantified by Technegas SPECT and 129Xe MRI were determined by Spearman correlation and Bland-Altman analysis, respectively. Results: VDP measured by Technegas SPECT and 129Xe MRI were correlated (VDPT: r = 0.48, p = 0.001; VDPK: r = 0.63, p < 0.0001). A 2.0% and 1.6% bias towards higher Technegas SPECT VDP was measured using the adaptive threshold method (VDPT: 23.0% ± 14.0% vs. 21.0% ± 5.2%, p = 0.81) and k-means method (VDPK: 9.4% ± 9.4% vs. 7.8% ± 10.0%, p = 0.02), respectively. For both modalities, higher VDP was correlated with lower FEV1/FVC (SPECT VDPT: r = -0.38, p = 0.01; MRI VDPK: r = -0.46, p = 0.002) and DLCO (SPECT VDPT: r = -0.61, p < 0.0001; MRI VDPK: r = -0.68, p < 0.0001). Subgroup analysis revealed that VDP measured by both modalities was significantly higher for participants with COPD (n = 13) than those with asthma (n = 6; SPECT VDPT: p = 0.007, MRI VDPK: p = 0.006) and those with no history of obstructive lung disease (n = 21; SPECT VDPT: p = 0.0003, MRI VDPK: p = 0.0003). Discussion: The burden of ventilation defects quantified by Technegas SPECT and 129Xe MRI VDP was correlated and greater in participants with COPD when compared to those without. Our observations indicate that, despite substantial differences between the imaging modalities, quantitative assessment of ventilation defects by Technegas SPECT and 129Xe MRI is comparable.

Molecular brain differences and cannabis involvement: A systematic review of positron emission tomography studies.

BACKGROUND: An increasing number of studies have used positron emission tomography (PET) to investigate molecular neurobiological differences in individuals who use cannabis. This study aimed to systematically review PET imaging research in individuals who use cannabis or have cannabis use disorder (CUD). METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria, a comprehensive systematic review was undertaken using the PubMed, Scopus, PsycINFO and Web of Science databases. RESULTS: In total, 20 studies were identified and grouped into three themes: (1) studies of the dopamine system primarily found that cannabis use was associated with abnormal striatal dopamine synthesis capacity, which was in turn correlated with clinical symptoms; (2) studies of the endocannabinoid system found that cannabis use and CUD are associated with lower cannabinoid receptor type 1 availability and global reductions in fatty acid amide hydrolase binding; (3) studies of brain metabolism found that individuals who use cannabis exhibit lower normalized glucose metabolism in both cortical and subcortical brain regions, and reduced cerebral blood flow in the lateral prefrontal cortex during experimental tasks. Heterogeneity across studies prevented meta-analysis. CONCLUSION: Existing PET imaging research reveals substantive molecular differences in cannabis users in the dopamine and endocannabinoid systems, and in global brain metabolism, although the heterogeneity of designs and approaches is very high, and whether these differences are causal versus consequential is largely unclear.

Safety and Efficacy of Alendronate to Treat Osteopenia in Children During Therapy for Acute Lymphoblastic Leukemia: A Retrospective Cohort Study of Sequential Outcomes.

BACKGROUND: Low bone mineral density is encountered in children with acute lymphoblastic leukemia (ALL) before, during, and after treatment. Prior experience with alendronate, an oral bisphosphonate, demonstrated high tolerability and evident clinical efficacy. However, concerns have been expressed about the long-term safety and utility of such agents in children. PROCEDURE: Sixty-nine children with ALL received alendronate for a mean of 87 weeks after dual-energy radiograph absorptiometry. Dual-energy radiograph absorptiometry was repeated following the completion of alendronate, and 5 to 9 years later in a subgroup of 32 children. Lumbar spine areal bone mineral density (LS aBMD) Z scores were obtained. RESULTS: The mean LS aBMD Z score rose from -1.78 to-0.47 ( P <0.0001). There was a modest median loss of LS aBMD subsequently in the 32 subjects on long-term follow-up. Almost 80% (N=172) of the children remain in continuous complete remission at a mean of 14.5 years from diagnosis. Of those who received alendronate, which was almost uniformly well tolerated, 7/69 (10.3%) relapsed compared with 19/89 (21.3%) who did not receive the drug. DISCUSSION: Alendronate appears to be well tolerated and moderately effective in osteopenic children with ALL. Whether it offers protection against relapse of leukemia needs further study.

The Influence of Body Composition on Bone Health in Long-term Survivors of Acute Lymphoblastic Leukemia in Childhood and Adolescence: Analyses by Dual-energy Radiograph Absorptiometry and Peripheral Quantitative Computed Tomography.

BACKGROUND: The normal interrelationship of body composition with bone health is less clear in the context of disease. Survivors of acute lymphoblastic leukemia (ALL) exhibit sarcopenic obesity and osteopenia. The impact of body composition on bone health in such survivors was examined. SUBJECTS AND METHODS: Survivors of ALL (N=74), >10 years from diagnosis, underwent dual-energy radiograph absorptiometry and peripheral quantitative computed tomography. RESULTS: Whole-body bone mineral content (WB BMC) Z scores were greater in males than females, but WB BMC indices (WB BMC/height 2 ) were comparable (0.74±0.125 and 0.72±0.069, respectively). WB BMC index (I) and fat-free mass index correlated significantly with trabecular bone mineral density, only in males. Fat mass index and appendicular lean mass index showed no such correlations. WB BMCI and fat-free mass index also correlated, again predominantly in males, with measures of strength in both trabecular and cortical bone. WB BMCI also correlated strongly with trabecular number, thickness, and hole size, also only in males. CONCLUSIONS: The results point to the need for enhancing muscle mass, measured by appendicular lean mass index, while reducing fat mass and maintaining good bone mineralization in long-term survivors of ALL to ensure the integrity of healthy bones.

Bone health in long-term survivors of pediatric acute lymphoblastic leukemia. An assessment by peripheral quantitative computed tomography.

BACKGROUND: Loss of bone mineral is a common concomitant of the treatment of acute lymphoblastic leukemia (ALL) due mainly to chemotherapy, especially with corticosteroids. Osteopenia/osteoporosis may be encountered long into survivorship. Measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry is limited to two-dimensionality and cannot distinguish trabecular from cortical bone. METHODS: A sample of 74 subjects, ages 13.5-38.3 years more than 10 years from diagnosis, underwent peripheral quantitative computed tomography (pQCT) at metaphyseal (trabecular bone) and diaphyseal (cortical bone) sites in the radius and tibia. pQCT provides three-dimensional assessment of bone geometry, density, and architecture. RESULTS: Average values in multiple metrics were similar to those in healthy individuals, but deficits in both trabecular and cortical bones were revealed by lower Z scores using an ethnically comparable sample of healthy individuals. Connectivity, a measure of bone architecture and a surrogate measure of bone strength, was lower in females than males. Survivors of standard-risk ALL had greater connectivity in and more compact trabecular bone than high-risk survivors who had received more intensive osteotoxic chemotherapy. There were no statistically significant differences in any of the metrics at any of the sites between subjects who had or had not a history of fracture, cranial irradiation, or use of a bisphosphonate. CONCLUSIONS: These long-term survivors of ALL have somewhat compromised bone health, but data in comparable healthy populations are limited. Longitudinal studies in larger and more ethnically diverse cohorts will provide greater insight into bone health in this vulnerable population.

Relationships of Bone Mineral Density to Whole Body Mass, Fat Mass and Fat-free Mass in Long-term Survivors of Acute Lymphoblastic Leukemia in Childhood.

Body size influences bone mineral density (BMD) in health. Relationships of BMD with body mass index, fat mass (FM), fat-free mass, and appendicular lean mass were explored in acute lymphoblastic leukemia (ALL) survivors (n=75; 41 males; 45 standard risk ALL) >10 years from diagnosis. Dual energy radiograph absorptiometry performed body composition analysis. Relationships were assessed by regression analyses and Pearson correlation coefficients (r). Twenty subjects (26.3%) were osteopenic; lumbar spine (LS) BMD Z score <-1.00. Age at diagnosis, sex, ALL risk-category, type of post-induction steroid or cranial radiation did not correlate with LS or whole body (WB) BMD. Body mass index correlated significantly with LS BMD (r=0.333, P=0.004) and WB BMD (r=0.271, P=0.033). FM index (FM/height²) Z score showed no significant correlation with LS or WB BMD. Fat-free mass index Z score correlated strongly with LS BMD (r=0.386, P=0.013) and WB BMD (r=0.605, P<0.001) in males but not in females. The appendicular lean mass index, a surrogate for skeletal muscle mass, correlated significantly with LS BMD (r=0.367, P=0.018) and WB BMD (r=0.604, P<0.001) in males but not in females. Future studies to evaluate interventions to enhance BMD focused on improving body composition particularly skeletal muscle mass are warranted.

Maternal and child factors associated with bone length traits in children at 3 years of age.

BACKGROUND: Exposure to sub-optimal maternal vitamin D status during pregnancy has been linked to inadequate in utero bone growth with potential for post-natal deficits, but reported findings are inconsistent. Possible reasons include measurement error in assessing bone length/height, or lack of adjustment for confounding variables such as maternal/infant diet, physical activity and season of birth. The objective of this study was to determine the maternal and child factors associated with bone length traits in children at 3 years of age as part of a longitudinal follow-up of a pregnancy cohort. METHODS: Mother-child dyads enrolled in the Family Atherosclerosis Monitoring In early Life study were included. Maternal serum 25-hydroxyvitamin D (25(OH)D) concentration was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Anthropometry, physical activity by questionnaire and dietary assessment by food frequency questionnaire were completed for mothers during pregnancy (27-40 weeks gestation) and for children at 3 years with diet by 3-day food records (Nutritionist Pro). Whole body bone mineral density in mother and child (n = 473) was measured by dual-energy absorptiometry (DXA) at the 3 year visit. A software program was developed using MATLAB to derive bone length measurements from whole body DXA images using 8 long bones of each child. Association between maternal and child variables with offspring bone length was assessed using unadjusted and adjusted multivariate linear regression analyses. RESULTS: In the final adjusted multivariate regression model, factors associated with child bone length were maternal height (p = 0.05), child birth length (p = 0.005) and child weight z-score at 3 years (p < 0.001). No association was observed between maternal serum 25(OH)D concentrations in pregnancy (of which 77% were in normal range) and child bone length. CONCLUSION: In healthy Canadian mothers and their children, the factors associated with child bone length achieved at 3 years of age appear to be related to genetic traits rather than environmental exposures. Measures of the length of long bones in children using DXA scans may have provided a more accurate assessment of bone length than whole body height measures.

The Dopamine Allosteric Agent, PAOPA, Demonstrates Therapeutic Potential in the Phencyclidine NMDA Pre-clinical Rat Model of Schizophrenia.

PAOPA, a potent analog of prolyl-leucyl-glycinamide, has shown therapeutic potential at the preclinical stage for dopaminergic related illnesses, including animal models of schizophrenia, Parkinson's disease and haloperidol-induced extrapyramidal movement disorders. PAOPA's unique allosteric mechanism and dopamine D2 receptor specificity provide a unique composition of properties for the development of potential therapeutics for neuropsychiatric illnesses. We sought to investigate PAOPA's therapeutic prospects across the spectrum of schizophrenia-like symptoms represented in the established phencyclidine-induced rat model of schizophrenia, (5 mg/kg PCP twice daily for 7 days, followed by 7 days of drug withdrawal). PAOPA was assessed for its effect on brain metabolic activity and across a battery of behavioral tests including, hyperlocomotion, social withdrawal, sensorimotor gating, and novel object recognition. PAOPA showed therapeutic efficacy in behavioral paradigms representing the negative (social withdrawal) and cognitive-like (novel object recognition) symptoms of schizophrenia. Interestingly, some behavioral indices associated with the positive symptoms of schizophrenia that were ameliorated in PAOPA's prior examination in the amphetamine-sensitized model of schizophrenia were not ameliorated in the PCP model; suggesting that the deficits induced by amphetamine and PCP-while phenotypically similar-are mechanistically different and that PAOPA's effects are restricted to certain mechanisms and systems. These studies provide insight on the potential use of PAOPA for the safe and effective treatment of schizophrenia.

Body composition in long-term survivors of acute lymphoblastic leukemia diagnosed in childhood and adolescence: A focus on sarcopenic obesity.

BACKGROUND: The late effects of treatment for acute lymphoblastic leukemia (ALL) include disordered body composition, especially obesity. Less attention has been focused on the loss of skeletal muscle mass (SMM) and the combined morbidity of sarcopenic obesity. METHODS: A cross-sectional study of body composition was undertaken via dual-energy x-ray absorptiometry in 75 long-term survivors of ALL (more than 10 years after the diagnosis). Measures were obtained of the fat mass (FM), fat-free mass (equivalent to the lean body mass [LBM]), and whole-body bone mineral content. Health-related quality of life (HRQL) was measured with the Health Utilities Index. RESULTS: The sum of the FM, LBM, and whole-body bone mineral content matched the total body weight measured directly (r = 0.998). The appendicular lean mass (ALM) was derived from the LBM in all 4 limbs and accounted for approximately 75% of the SMM. According to the fat mass index (FMI; ie, FM/height2 ), 12% of females and 18% of males were frankly obese by World Health Organization criteria. The median FMI z score was + 0.40, whereas the median z score for the appendicular lean mass index (ALMI; ie, ALM/height2 ) was -0.40. Sarcopenic obesity, defined as a positive FMI z score with a negative ALMI z score, was present in 32 subjects (43%). There were statistically significant and clinically important differences in overall HRQL between subjects with and without sarcopenic obesity. CONCLUSIONS: Sarcopenic obesity is prevalent in long-term survivors of ALL, and this places them in double jeopardy from excess body fat and inadequate SMM (eg, a combination of metabolic and frailty syndromes). It is associated with an adverse impact on overall HRQL. Cancer 2018;124:1225-31. © 2017 American Cancer Society.

Characterization of 3-Dimensional PET Systems for Accurate Quantification of Myocardial Blood Flow.

Three-dimensional (3D) mode imaging is the current standard for PET/CT systems. Dynamic imaging for quantification of myocardial blood flow with short-lived tracers, such as 82Rb-chloride, requires accuracy to be maintained over a wide range of isotope activities and scanner counting rates. We proposed new performance standard measurements to characterize the dynamic range of PET systems for accurate quantitative imaging. METHODS: 82Rb or 13N-ammonia (1,100-3,000 MBq) was injected into the heart wall insert of an anthropomorphic torso phantom. A decaying isotope scan was obtained over 5 half-lives on 9 different 3D PET/CT systems and 1 3D/2-dimensional PET-only system. Dynamic images (28 × 15 s) were reconstructed using iterative algorithms with all corrections enabled. Dynamic range was defined as the maximum activity in the myocardial wall with less than 10% bias, from which corresponding dead-time, counting rates, and/or injected activity limits were established for each scanner. Scatter correction residual bias was estimated as the maximum cavity blood-to-myocardium activity ratio. Image quality was assessed via the coefficient of variation measuring nonuniformity of the left ventricular myocardium activity distribution. RESULTS: Maximum recommended injected activity/body weight, peak dead-time correction factor, counting rates, and residual scatter bias for accurate cardiac myocardial blood flow imaging were 3-14 MBq/kg, 1.5-4.0, 22-64 Mcps singles and 4-14 Mcps prompt coincidence counting rates, and 2%-10% on the investigated scanners. Nonuniformity of the myocardial activity distribution varied from 3% to 16%. CONCLUSION: Accurate dynamic imaging is possible on the 10 3D PET systems if the maximum injected MBq/kg values are respected to limit peak dead-time losses during the bolus first-pass transit.

A Kernel Density Estimator-Based Maximum A Posteriori Image Reconstruction Method for Dynamic Emission Tomography Imaging.

A novel maximum a posteriori (MAP) method for dynamic single-photon emission computed tomography image reconstruction is proposed. The prior probability is modeled as a multivariate kernel density estimator (KDE), effectively modeling the prior probability non-parametrically, with the aim of reducing the effects of artifacts arising from inconsistencies in projection measurements in low-count regimes where projections are dominated by noise. The proposed prior spatially and temporally limits the variation of time-activity functions (TAFs) and attracts similar TAFs together. The similarity between TAFs is determined by the spatial and range scaling parameters of the KDE-like prior. The resulting iterative image reconstruction method is evaluated using two simulated phantoms, namely the extended cardiac-torso (XCAT) heart phantom and a simulated Mini-Deluxe Phantom. The phantoms were chosen to observe the effects of the proposed prior on the TAFs based on the vicinity and abutments of regions with different activities. Our results show the effectiveness of the proposed iterative reconstruction method, especially in low-count regimes, which provides better uniformity within each region of activity, significant reduction of spatiotemporal variations caused by noise, and sharper separation between different regions of activity than expectation maximization and an MAP method employing a more traditional Gibbs prior.

A standardized infrared imaging technique that specifically detects UCP1-mediated thermogenesis in vivo.

The activation and expansion of brown adipose tissue (BAT) has emerged as a promising strategy to counter obesity and the metabolic syndrome by increasing energy expenditure. The subsequent testing and validation of novel agents that augment BAT necessitates accurate pre-clinical measurements in rodents regarding the capacity for BAT-derived thermogenesis. We present a novel method to measure BAT thermogenesis using infrared imaging following ß3-adrenoreceptor stimulation in mice. We show that the increased body surface temperature observed using this method is due solely to uncoupling protein-1 (UCP1)-mediated thermogenesis and that this technique is able to discern differences in BAT activity in mice acclimated to 23 °C or thermoneutrality (30 °C). These findings represent the first standardized method utilizing infrared imaging to specifically detect UCP1 activity in vivo.

Correlative single photon emission computed tomography imaging of [123I]altropane binding in the rat model of Parkinson's.

INTRODUCTION: This study used the dopamine transporter (DAT) probe, [(123)I]-2ß-carbomethoxy-3ß-(4-fluorophenyl)-N-(3-iodo-E-allyl)nortropane ([(123)I]altropane), to assess the DAT levels in the 6-hydroxydopamine rat model of Parkinson's disease. We sought to assess if the right to left [(123)I]altropane striatal ratios correlated with dopamine content in the striatum and substantia nigra and with behavioural outcomes. METHODS: [(123)I]altropane images taken pre- and postlesion were acquired before and after the transplantation of neural stem/progenitor cells. The images obtained using [(123)I]altropane and single photon emission computed tomography (SPECT) were compared with specific behavioural tests and the dopamine content assessed by high-performance liquid chromatography. RESULTS: [(123)I]altropane binding correlated with the content of dopamine in the striatum; however, [(123)I]altropane binding did not correlate with the dopamine content in the substantia nigra. There was a significant correlation of altropane ratios with the cylinder test and the postural instability test, but not with amphetamine rotations. The low coefficient of determination (r(2)) for these correlations indicated that [(123)I]altropane SPECT was not a good predictor of behavioural outcomes. CONCLUSION: Our data reveal that [(123)I]altropane predicts the integrity of the striatal dopamine nerve terminals, but does not predict the integrity of the nigrostriatal system. [(123)I]altropane could be a useful marker to measure dopamine content in cell replacement therapies; however, it would not be able to evaluate outcomes for neuroprotective strategies.

An evaluation of iterative reconstruction strategies based on mediastinal lesion detection using hybrid Ga-67 SPECT images.

Using psychophysical studies, the authors have evaluated the effectiveness of various strategies for compensating for physical degradations in SPECT imaging. The particular application was Ga-67-citrate imaging of mediastinal tumors, which was chosen because Ga-67 is a particularly challenging radionuclide for imaging. The test strategies included compensations for nonuniform attenuation, distance-dependent spatial resolution, and scatter applied in various combinations as part of iterative reconstructions with the rescaled block iterative-expectation maximization (RBI-EM) algorithm. The authors also evaluated filtered backprojection reconstructions. Strategies were compared on the basis of human-observer studies of lesion localization and detection accuracy using the localization receiver operating characteristics (LROC) paradigm. These studies involved hybrid images which were obtained by adding the projections of Monte Carlo-simulated lesions to disease-free clinical projection data. The background variability in these images can provide a more realistic assessment of the relative utility of reconstruction strategies than images from anthropomorphic digital phantoms. The clinical datasets were obtained using a GE-VG dual-detector SPECT system with CT-estimated attenuation maps. After determining a target lesion contrast, they conducted pilot LROC studies to obtain a near-optimal set of reconstruction parameters for each strategy, and then conducted the strategy comparison study. The results indicate improved detection accuracy with RBI-EM as more compensations are applied within the reconstruction. The relative rankings of the test strategies agreed in most cases with those of previous studies that employed simulated projections of digital anthropomorphic phantoms, thus confirming the findings of those studies.

Comparison between conventional and "clinical" assessment of experimental lung fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a treatment resistant disease with poor prognosis. Numerous compounds have been demonstrated to efficiently prevent pulmonary fibrosis (PF) in animal models but only a few were successful when given to animals with established fibrosis. Major concerns of current PF models are spontaneous resolution and high variability of fibrosis, and the lack of assessment methods that can allow to monitor the effect of drugs in individual animals over time. We used a model of experimental PF in rats and compare parameters obtained in living animals with conventional assessment tools that require removal of the lungs. METHODS: PF was induced in rats by adenoviral gene transfer of transforming growth factor-beta. Morphological and functional changes were assessed for up to 56 days by micro-CT, lung compliance (measured via a mechanical ventilator) and VO2max and compared to histomorphometry and hydroxyproline content. RESULTS: Standard histological and collagen assessment confirmed the persistent fibrotic phenotype as described before. The histomorphological scores correlated both to radiological (r2 = 0.29, p < 0.01) and functional changes (r2 = 0.51, p < 0.0001). VO2max did not correlate with fibrosis. CONCLUSION: The progression of pulmonary fibrosis can be reliably assessed and followed in living animals over time using invasive, non-terminal compliance measurements and micro-CT. This approach directly translates to the management of patients with IPF and allows to monitor therapeutic effects in drug intervention studies.

Isostructural fluorescent and radioactive probes for monitoring neural stem and progenitor cell transplants.

A construct for tagging neurospheres and monitoring cell transplantations was developed using a new technology for producing luminescent and radiolabeled probes that have identical structures. The HIV1-Tat basic domain derivatives NAcGRKKRRQRRR(SAACQ)G (SAACQ-1) and [NAcGRKKRRQRRR(Re(CO)3SAACQ)G]+ (ReSAACQ-1) were prepared in excellent yields using the single amino acid chelate-quinoline (SAACQ) ligand and its Re(I) complex and conventional automated peptide synthesis methods. The distribution of the luminescent Re probe, using epifluorescence microscopy, showed that it localized primarily in the cell nucleus with a significant degree of association on the nuclear envelope. A smaller amount was found to be dispersed in the cytoplasm. The 99m Tc analogue was then prepared in 43+/-7% (n=12) yield and very high effective specific activity. Following incubation, average uptake of the probe in neurospheres ranged between 10 and 20 Bq/cell. As determined by colorimetric assays, viability for cells labeled with high effective specific activity 99m TcSAACQ-1 was 97+/-4% at 2 h postlabeling and 85+/-25% at 24 h postlabeling for incubation activities ranging from 245 to 8900 Bq/cell. DNA analysis showed that at these levels, there was no significant difference between the extent of DNA damage in the treated cells versus control cells. A series of preliminary SPECT/CT studies of transplants in mice were performed, which showed that the strategy is convenient and feasible and that it is possible to routinely assess procedures noninvasively and determine the number of cells transplanted.

Accelerated SPECT Monte Carlo Simulation Using Multiple Projection Sampling and Convolution-Based Forced Detection.

Monte Carlo (MC) is a well-utilized tool for simulating photon transport in single photon emission computed tomography (SPECT) due to its ability to accurately model physical processes of photon transport. As a consequence of this accuracy, it suffers from a relatively low detection efficiency and long computation time. One technique used to improve the speed of MC modeling is the effective and well-established variance reduction technique (VRT) known as forced detection (FD). With this method, photons are followed as they traverse the object under study but are then forced to travel in the direction of the detector surface, whereby they are detected at a single detector location. Another method, called convolution-based forced detection (CFD), is based on the fundamental idea of FD with the exception that detected photons are detected at multiple detector locations and determined with a distance-dependent blurring kernel. In order to further increase the speed of MC, a method named multiple projection convolution-based forced detection (MP-CFD) is presented. Rather than forcing photons to hit a single detector, the MP-CFD method follows the photon transport through the object but then, at each scatter site, forces the photon to interact with a number of detectors at a variety of angles surrounding the object. This way, it is possible to simulate all the projection images of a SPECT simulation in parallel, rather than as independent projections. The result of this is vastly improved simulation time as much of the computation load of simulating photon transport through the object is done only once for all projection angles.The results of the proposed MP-CFD method agrees well with the experimental data in measurements of point spread function (PSF), producing a correlation coefficient (r(2)) of 0.99 compared to experimental data. The speed of MP-CFD is shown to be about 60 times faster than a regular forced detection MC program with similar results.

Convolution-Based Forced Detection Monte Carlo Simulation Incorporating Septal Penetration Modeling.

In SPECT imaging, photon transport effects such as scatter, attenuation and septal penetration can negatively affect the quality of the reconstructed image and the accuracy of quantitation estimation. As such, it is useful to model these effects as carefully as possible during the image reconstruction process. Many of these effects can be included in Monte Carlo (MC) based image reconstruction using convolution-based forced detection (CFD). With CFD Monte Carlo (CFD-MC), often only the geometric response of the collimator is modeled, thereby making the assumption that the collimator materials are thick enough to completely absorb photons. However, in order to retain high collimator sensitivity and high spatial resolution, it is required that the septa be as thin as possible, thus resulting in a significant amount of septal penetration for high energy radionuclides. A method for modeling the effects of both collimator septal penetration and geometric response using ray tracing (RT) techniques has been performed and included into a CFD-MC program. Two look-up tables are pre-calculated based on the specific collimator parameters and radionuclides, and subsequently incorporated into the SIMIND MC program. One table consists of the cumulative septal thickness between any point on the collimator and the center location of the collimator. The other table presents the resultant collimator response for a point source at different distances from the collimator and for various energies. A series of RT simulations have been compared to experimental data for different radionuclides and collimators. Results of the RT technique matches experimental data of collimator response very well, producing correlation coefficients higher than 0.995. Reasonable values of the parameters in the lookup table and computation speed are discussed in order to achieve high accuracy while using minimal storage space for the look-up tables. In order to achieve noise-free projection images from MC, it is seen that the inclusion of the RT implementation for septal penetration increases the speed of the simulation by a factor of about 7,500 compared to the conventional SIMIND MC program.