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Techniques to estimate dynamic parameters from the data acquired during a single rotation of a standard (single, dual and triple head) SPECT camera are being investigated. The performance of the constrained linear least squares (C-LS) method is being assessed. This method uses a simple assumption that the activity within each pixel at a given projection angle is less than or equal to the activity seen at the prior angle. In simulations, we have used an analytical heart model with single and bi-exponential activity decrease, with and without background activity and statistical noise in the data. Studies using a single, a 90 [degrees] dual and a 120 [degrees] triple head camera were modeled with a total acquisition time of 20min, performing rotation over 180 [degrees] . These simulations were followed by experimental scans of our dynamic phantom used with and without attenuation and subsequently a preliminary study involving a human subject was performed. Dynamic images from simulations and phantom experiments reconstruct well with an accuracy of reconstructed half-lives for most reconstructions within a 20% error range. Some streaking artifacts which are evident in images corresponding to early reconstruction times subside upon incorporating further constraints and regularizations.

We have designed and built a dynamic heart-in-thorax phantom to be used as the primary tool for experimental verification of a quantitative dynamic functional imaging method we are developing for standard rotating single photon emission computed tomography (SPECT) cameras. The phantom consists of two independent parts (i) a dynamic heart model which allows up to two 'defects' to be mounted inside it and, (ii) a non-uniform thorax model with lungs and spinal cord. The principle behind the design of the phantom is the fact that the washout of a tracer by dilution is governed by a linear first order equation, the same type of equation as is used to model time-activity distribution in myocardial viability studies. Tests of the dynamic performance of the phantom using the planar scanning mode have confirmed the validity of these assumptions. Also the preliminary results obtained from dynamic data acquired using a simplified version of the phantom in SPECT mode show that the values of characteristic times could be experimentally determined and that these values agreed well with the values preset on the phantom. We consider that the phantom is ready for use in the development of the dynamic SPECT method.

Dynamic SPECT (dSPECT) is an image reconstruction method capable of determining three dimensional regional estimates of physiological kinetic rates while still maintaining the simple acquisition protocol of a single, slow camera rotation. Through the use of inequality constraints in a least squares optimization routine, we are able to determine both the rate of tracer uptake and subsequent tracer washout over the acquisition time of the SPECT scan. Simulations modelling different camera acquisition geometries and with variable dual exponential kinetic parameters and model complexity (eg, statistical noise, object attenuation) were performed. It was found that kinetic parameters were accurate to within 50% of the true values for the case of fast uptake and slow washout for a single head acquisition and improved to within 95% when acquired with a triple, head camera. Experimental phantom tests corraborated these results and are shown to have an accuracy of about 90%. A preliminary patient study of renal dynamics has also been performed and compared with conventional planar dynamic imaging. Results from this study indicate that the dSPECT reconstruction method is able to determine kinetic information with accuracy comparable to that of conventional planar dynamic imaging methods while providing additional three dimensional time behaviour information.

In volumetric CT imaging of small animals, the breathing motion of the lungs during the image acquisition process results in inconsistent projection data being acquired. When reconstructed, these inconsistent data may produce images with reduced spatial resolution and image contrast. In order to minimize these effects, various approaches have been utilized to capture the respiratory signal of the animals under study and to only obtain CT data at specific moments in the respiratory cycle. These approaches typically utilize hardware-based physiological monitoring equipment in order to record the respiratory signal and either prospectively or retrospectively correlate this signal with acquired CT projection data. In this work, a new method of CT respiratory gating is described that does not rely on external physiological monitoring. Rather, determination of the respiratory phase of the animal is performed by postprocessing the acquired projection data. With this approach, any CT projection data can be respiratory gated with minimal effort. Validation of the method has been performed using a dynamic phantom and accuracy in tidal volumes determined to be within 16%. Rats and mice have been scanned and processed using the proposed method and compared to physiological-based measurement. With the proposed method, image quality is significantly improved in addition to providing quantitative information regarding tidal lung volumes. [ABSTRACT FROM AUTHOR]

In pelvic bone SPECT using Tc-99m labeled compounds, physical effects such as nonhomogeneous attenuation and the accumulation of activity into the bladder during the data acquisition process can often result in data inconsistencies. With filtered backprojection (FBP) reconstruction, this may result in streak artifacts. Various methods for attenuation compensation can be employed to account for some of these streaks, but if the rate of uptake of tracer in to the bladder is sufficient, the resultant streaks may be significant enough to impair lesion detection. We have investigated various reconstruction methods in an effort to reduce these artifacts. In order to assess the impact of inconsistent bladder activities on the detection of pelvic lesions, SPECT imaging was simulated using the Zubal voxelized phantom, for cases of both a static bladder activity and a changing activity distribution. Reconstructions were performed using FBP, ordered subset-expectation maximization (OSEM) and dynamic expectation maximization (dEM) and was assessed for lesion detectability using a channelized, nonprewhitening (CNPW) numerical observer model. This observer model was used to optimize reconstruction strategies for a human LROC observer study. The human LROC observer study was performed in order to assess the various reconstruction methods in terms of lesion detectability. Three human observers were used in this test. The results of this test indicate that FBP performs significantly worse than static OSEM iterative reconstruction with attenuation correction when assessed using the area under the LROC curve (maximal ALROC: = 0.47 for FBP versus 0.71 for OSEM). Visually, the dEM algorithm produces images with slightly reduced streak artifacts compared to OSEM, but this improvement was not reflected in significantly improved ALROC values. In fact, when assessed using human LROC methodology, detectability actually decreased slightly when using dEM (maximal ALROC = 0.71 for OSEM versus 0.66 for dEM), although this reduction was not determined to be statistically significant. It is possible that the slightly reduced performance of the dEM algorithm may be due, in part, to not performing an optimization in the number of reconstruction iterations as was performed for the OSEM method. [ABSTRACT FROM AUTHOR]

Abstract 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.

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.

Background: Sarcopenia, a loss of systemic skeletal muscle mass (SMM), is prevalent in childhood cancer survivors and often accompanied by increased fat mass (sarcopenic obesity [SO]). We examined whether calf muscle cross-sectional area (CSA), measured by peripheral quantitative computed tomography (pQCT), can identify sarcopenia and SO in long-term survivors of pediatric acute lymphoblastic leukemia (ALL), and explored its relationship with adjacent bone geometry., Procedures: Calf muscle CSA and CSA Z scores at the 38% tibia in 70 subjects (median survival 15 years) were compared between sexes and ALL risk group, and their association with sarcopenia and SO evaluated. Relationships between bone strength and muscle mass were assessed further using linear regression and methods described by Schoenau et al. for evaluation of a functional muscle-bone unit., Results: A calf muscle CSA Z score of less than or equal to zero is 73.81% sensitive and 84.62% specific for detecting sarcopenia defined by height-adjusted appendicular lean mass measured by dual-energy x-ray absorptiometry. No significant difference in CSA Z scores was noted between sexes or ALL risk groups; however, Z scores were markedly higher in those without SO (adjusted odds ratio 0.529, 95% confidence interval [CI]: 0.340-0.824). Ratios of calf muscle mass to height and total bone mineral content at the 38% tibia are "sufficient" and consistent with estimated reference ranges for a healthy population., Conclusions: CSA Z scores may represent a useful clinical measure of SMM and are predictive of SO in this population. Our results are supportive of a functional muscle-bone unit in long-term survivors of pediatric ALL., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

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., Competing Interests: Declaration of competing interest James MacKillop is a Principal and Senior Scientist in BEAM Diagnostics, Inc. and a Consultant to Clairvoyant Therapeutics, Inc. No other authors have conflicts of interest to report., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors have no conflicts of interest to declare, (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The ideal contrast agents for ventilation SPECT and MRI are Technegas and 129 Xe 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 129 Xe 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 129 Xe MRI, spirometry, and diffusing capacity of the lung for carbon monoxide (DL CO ). Ventilation abnormalities were quantified as the VDP using two different methods: adaptive thresholding (VDP T ) and k-means clustering (VDP K ). Correlation and agreement between VDP quantified by Technegas SPECT and 129 Xe MRI were determined by Spearman correlation and Bland-Altman analysis, respectively. Results: VDP measured by Technegas SPECT and 129 Xe MRI were correlated (VDP T : r = 0.48, p = 0.001; VDP K : 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 (VDP T : 23.0% ± 14.0% vs. 21.0% ± 5.2%, p = 0.81) and k-means method (VDP K : 9.4% ± 9.4% vs. 7.8% ± 10.0%, p = 0.02), respectively. For both modalities, higher VDP was correlated with lower FEV 1 /FVC (SPECT VDP T : r = -0.38, p = 0.01; MRI VDP K : r = -0.46, p = 0.002) and DL CO (SPECT VDP T : r = -0.61, p < 0.0001; MRI VDP K : 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 VDP T : p = 0.007, MRI VDP K : p = 0.006) and those with no history of obstructive lung disease (n = 21; SPECT VDP T : p = 0.0003, MRI VDP K : p = 0.0003). Discussion: The burden of ventilation defects quantified by Technegas SPECT and 129 Xe 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 129 Xe MRI is comparable., Competing Interests: The authors declare that this was an investigator-initiated study that received funding from Cyclomedica Australia Pty Ltd. and The Lung Association. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. SS reports a relationship with Polarean that includes: Speaking and lecture fees. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Radadia, Friedlander, Priel, Konyer, Huang, Jamal, Farncombe, Marriott, Finley, Agzarian, Dolovich, Noseworthy, Nair, Shargall and Svenningsen.)

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2021 Wiley Periodicals LLC.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

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 82 Rb-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: 82 Rb or 13 N-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., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Preclinical imaging allows pulmonary researchers to study lung disease and pulmonary drug delivery noninvasively and longitudinally in small animals. However, anatomically localizing a pathology or drug deposition to a particular lung region is not easily done. Thus, a detailed knowledge of the anatomical structure of small animal lungs is necessary for understanding disease progression and in addition would facilitate the analysis of the imaging data, mapping drug deposition and relating function to structure. In this study, contrast-enhanced micro-computed tomography (CT) of the lung produced high-resolution images that allowed for the characterization of the rodent airway and pulmonary vasculature. Contrast-enhanced micro-CT was used to visualize the airways and pulmonary vasculature in Sprague-Dawley rats (200-225 g) and BALB/c mice (20-25 g) postmortem. Segmented volumes from these images were processed to yield automated measurements of the airways and pulmonary vasculature. The diameters, lengths, and branching angles of the airway, arterial, and venous trees were measured and analyzed as a function of generation number and vessel diameter to establish rules that could be applied at all levels of tree hierarchy. In the rat, airway, arterial, and venous tress were measured down to the 20th, 16th, and 14th generation, respectively. In the mouse, airway, arterial, and venous trees were measured down to the 16th, 8th, and 7th generation, respectively. This structural information, catalogued in a rodent database, will increase our understanding of lung structure and will aid in future studies of the relationship between structure and function in animal models of disease.

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.

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.

Hybrid LROC studies can be used to more realistically assess the impact of reconstruction strategies, compared to those constructed with digital phantoms. This is because hybrid data provides the background variability that is present in clinical imaging, as well as, control over critical imaging parameters, required to conduct meaningful tests. Hybrid data is obtained by adding Monte Carlo simulated lesions to disease free clinical projection data. Due to Ga-67 being a particularly challenging radionuclide for imaging, we use Ga-67 hybrid SPECT data to study the effectiveness of the various correction strategies developed to account for degradations in SPECT imaging. Our data was obtained using GE-VG dual detector SPECT-CT camera. After determining a target lesion contrast we conduct pilot LROC studies to obtain a near-optimal set of reconstruction parameters for the different strategies individually. These near-optimal parameters are then used to reconstruct the final evaluation study sets. All LROC study results reported here were obtained employing human observers only. We use final LROC study results to assess the impact of attenuation compensation, scatter compensation and detector resolution compensation on data reconstructed with the RBI-EM algorithm. We also compare these with FBP reconstructions of the same dataset. Our experiment indicates an improvement in detection accuracy, as various degradations inherent in the image acquisition process are compensated for in the reconstruction process.