Single Photon Emission Computed Tomography Research Articles

Efficient bone marrow irradiation and low uptake by non-haematological organs with an yttrium-90-anti-CD66 antibody prior to haematopoietic stem cell transplantation

We report the results of a Phase I radiation dose escalation study using an yttrium-90 (90Y) labelled anti-CD66 monoclonal antibody given with standard conditioning regimen for patients receiving haematopoietic stem cell transplants for myeloid leukaemia or myeloma. The 90Y-labelled anti-CD66 was infused prior to standard conditioning. In total, 30 patients entered the trial and 29 received 90Y-labelled mAb, at infused radiation activity levels of 5, 10, 25, or 37.5 megaBequerel (MBq)/kg lean body weight. A prerequisite for receiving the 90Y-labelled mAb was favourable dosimetry determined by single-photon emission computerised tomography (SPECT) dosimetry following administration of indium-111 (111In) anti-CD66. Estimated absorbed radiation doses delivered to the red marrow demonstrated a linear relationship with the infused activity of 90Y-labelled mAb. At the highest activity level of 37.5 MBq/kg, mean estimated radiation doses for red marrow, liver, spleen, kidneys and lungs were 24.6 ± 5.6 Gy, 5.8 ± 2.7 Gy, 19.1 ± 8.0 Gy, 2.1 ± 1.1 and 2.2 ± 0.9, respectively. All patients engrafted, treatment-related mortality 1-year post-transplant was zero. Toxicities were no greater than those anticipated for similar conditioning regimens without targeted radiation. The ability to substantially intensify conditioning prior to haematopoietic stem cell transplantation without increasing toxicity warrants further testing to determine efficacy. clinicaltrials.gov identifier: NCT01521611.

Neuropathologic Validation and Diagnostic Accuracy of Presynaptic Dopaminergic Imaging in the Diagnosis of Parkinsonism.

Degeneration of the presynaptic nigrostriatal dopaminergic system is one of the main biological features of Parkinson disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), which can be measured using single-photon emission CT imaging for diagnostic purposes. Despite its widespread use in clinical practice and research, the diagnostic properties of presynaptic nigrostriatal dopaminergic (DAT) imaging in parkinsonism have never been evaluated against the diagnostic gold standard of neuropathology. The aim of this study was to evaluate the diagnostic parameters of DAT imaging compared with pathologic diagnosis in patients with parkinsonism. Retrospective cohort study of patients with DAT imaging for the investigation of a clinically uncertain parkinsonism with brain donation between 2010 and 2021 to the Queen Square Brain Bank (London). Patients with DAT imaging for investigation of pure ataxia or dementia syndromes without parkinsonism were excluded. Those with a pathologic diagnosis of PD, MSA, PSP, or CBD were considered presynaptic dopaminergic parkinsonism, and other pathologies were considered postsynaptic for the analysis. DAT imaging was performed in routine clinical practice and visually classified by hospital nuclear medicine specialists as normal or abnormal. The results were correlated with neuropathologic diagnosis to calculate diagnostic accuracy parameters for the diagnosis of presynaptic dopaminergic parkinsonism. All of 47 patients with PD, 41 of 42 with MSA, 68 of 73 with PSP, and 6 of 10 with CBD (sensitivity 100%, 97.6%, 93.2%, and 60%, respectively) had abnormal presynaptic dopaminergic imaging. Eight of 17 patients with presumed postsynaptic parkinsonism had abnormal scans (specificity 52.9%). DAT imaging has very high sensitivity and negative predictive value for the diagnosis of presynaptic dopaminergic parkinsonism, particularly for PD. However, patients with CBD, and to a lesser extent PSP (of various phenotypes) and MSA (with predominant ataxia), can show normal DAT imaging. A range of other neurodegenerative disorders may have abnormal DAT scans with low specificity in the differential diagnosis of parkinsonism. DAT imaging is a useful diagnostic tool in the differential diagnosis of parkinsonism, although clinicians should be aware of its diagnostic properties and limitations. This study provides Class II evidence that DAT imaging does not accurately distinguish between presynaptic dopaminergic parkinsonism and non-presynaptic dopaminergic parkinsonism.

Determinants of successful ictal SPECT injection in phase 1 epilepsy presurgical evaluation: Findings from the pediatric epilepsy research consortium surgery database project.

The main goal of presurgical evaluation in drug-resistant focal epilepsy is to identify a seizure onset zone (SOZ). Of the noninvasive, yet resource-intensive tests available, ictal single-photon emission computed tomography (SPECT) aids SOZ localization by measuring focal increases in blood flow within the SOZ via intravenous peri-ictal radionuclide administration. Recent studies indicate that geographic and center-specific factors impact utilization of these diagnostic procedures. Our study analyzed successful ictal SPECT acquisition (defined as peri-ictal injection during inpatient admission) using surgery-related data from the Pediatric Epilepsy Research Consortium (PERC) surgery database. We hypothesized that a high seizure burden, longer duration of video EEG monitoring (VEEG), and more center-specific hours of SPECT availability would increase the likelihood of successful ictal SPECT. We identified study participants (≤18 years of age) who underwent SPECT as part of their phase 1 VEEG from January 2018 to June 2022. We assessed association between ictal SPECT outcomes (success vs. failure) and variables including patient demographics, epilepsy history, and center-specific SPECT practices. Phase 1 VEEG monitoring with ictal SPECT injection was planned in 297 participants and successful in 255 participants (85.86%). On multivariable analysis, the likelihood of a successful SPECT injection was higher in patients of non-Hispanic ethnicity (p = 0.040), shorter duration VEEG (p = 0.004), and higher hours of available SPECT services (p < 0.001). Higher seizure frequency (p = 0.033) was significant only in bivariate analysis. Patients treated at centers with more operational hours were more likely to experience pre-admission protocols prior to VEEG (p = 0.002). There is inter-center variability in protocols and SPECT acquisition capabilities. Shorter duration of EEG monitoring, non-Hispanic ethnicity (when on private insurance), extended operational hours of nuclear medicine as noted on multivariate analysis and higher seizure frequency in bivariate analysis are strongly associated with successful ictal SPECT injection. In pediatric patients with drug-resistant epilepsy, single-photon emission computed tomography (SPECT) scans can be helpful in localizing seizure onset zone. However, due to many logistical challenges described below, which include not only the half-life of the technetium isotope used to inject intravenously during a seizure (called the ictal SPECT scan) but also available nuclear scanner time in addition to the unpredictability of seizures, obtaining an ictal SPECT during a planned elective inpatient hospital stay is not guaranteed. Thus, as healthcare costs increase, planning a prolonged hospital stay during which an ictal SPECT scan is not feasible is not optimal. We leveraged our prospective surgery database to look at center-specific factors and patient-specific factors associated with an ictal SPECT injection in the first, pediatric-focussed, large-scale, multicenter, prospective, SPECT feasibility study. We found that longer availability of the scanner is the most important center-specific factor in assuring ictal SPECT injection. Although seizure frequency is an important patient-specific factor on bivariate analysis, this factor lost statistical significance when other factors like patient insurance status and video EEG duration were also considered in our multivariable logistical model.

Correction of multiplexing artefacts in multi-pinhole SPECT through temporal shuttering, de-multiplexing of projections, and alternating reconstruction

Objective. Single-photon emission computed tomography (SPECT) with pinhole collimators can provide high-resolution imaging, but is often limited by low sensitivity. Acquiring projections simultaneously through multiple pinholes affords both high resolution and high sensitivity. However, the overlap of projections from different pinholes on detectors, known as multiplexing, has been shown to cause artefacts which degrade reconstructed images. Approach. Multiplexed projection sets were considered here using an analytic simulation model of AdaptiSPECT-C—a brain-dedicated multi-pinhole SPECT system. AdaptiSPECT-C has fully adaptable aperture shutters, so can acquire projections with a combination of multiplexed and non-multiplexed frames using temporal shuttering. Two strategies for reducing multiplex artefacts were considered: an algorithm to de-multiplex projections, and an alternating reconstruction strategy for projections acquired with a combination of multiplexed and non-multiplexed frames. Geometric and anthropomorphic digital phantoms were used to assess a number of metrics. Main results. Both de-multiplexing strategies showed a significant reduction in image artefacts and improved fidelity, image uniformity, contrast recovery and activity recovery (AR). In all cases, the two de-multiplexing strategies resulted in superior metrics to those from images acquired with only mux-free frames. The de-multiplexing algorithm provided reduced image noise and superior uniformity, whereas the alternating strategy improved contrast and AR. Significance. The use of these de-multiplexing algorithms means that multi-pinhole SPECT systems can acquire projections with more multiplexing without degradation of images.

Establishment and validation of novel predictive models to predict bone metastasis in newly diagnosed prostate adenocarcinoma based on single-photon emission computed tomography radiomics.

To establish and validate novel predictive models for predicting bone metastasis (BM) in newly diagnosed prostate adenocarcinoma (PCa) via single-photon emission computed tomography radiomics. In a retrospective review of the clinical single-photon emission computed tomography (SPECT) database, 176 patients (training set: n = 140; validation set: n = 36) who underwent SPECT/CT imaging and were histologically confirmed to have newly diagnosed PCa from June 2016 to June 2022 were enrolled. Radiomic features were extracted from the region of interest (ROI) in a targeted lesion in each patient. Clinical features, including age, total prostate-specific antigen (t-PSA), and Gleason grades, were included. Statistical tests were then employed to eliminate irrelevant and redundant features. Finally, four types of optimized models were constructed for the prediction. Furthermore, fivefold cross-validation was applied to obtain sensitivity, specificity, accuracy, and area under the curve (AUC) for performance evaluation. The clinical usefulness of the multivariate models was estimated through decision curve analysis (DCA). A radiomics signature consisting of 27 selected features which were obtained by radiomics' LASSO treatment was significantly correlated with bone status (P < 0.01 for both training and validation sets). Collectively, the models showed good predictive efficiency. The AUC values ranged from 0.87 to 0.98 in four models. The AUC values of the human experts were 0.655 and 0.872 in the training and validation groups, respectively. Most radiomic models showed better diagnostic accuracy than human experts in the training and validation groups. DCA also demonstrated the superiority of the radiomics models compared to human experts. Radiomics models are superior to humans in differentiating between benign bone and prostate cancer bone metastases; it can be used to facilitate personalized prediction of BM in newly diagnosed PCa patients.

Absolute quantitation of sympathetic nerve activity using [123I] metaiodobenzylguanidine SPECT-CT in neurology

Background and purposeThe ability of [123I]metaiodobenzylguanidine (MIBG) sympathetic nerve imaging with three-dimensional (3D) quantitation to clinically diagnose neurological disorders has not been evaluated. This study compared absolute heart counts calculated as mean standardized uptake values (SUVmean) using conventional planar imaging and assessed the contribution of [123I]MIBG single-photon emission computed tomography (SPECT)-CT to the diagnosis of neurological diseases.MethodsSeventy-two patients with neurological diseases were consecutively assessed using early and delayed [123I]MIBG SPECT-CT and planar imaging. Left ventricles were manually segmented in early and delayed SPECT-CT images, then the SUVmean and washout rates (WRs) were calculated. Heart-to-mediastinum ratios (HMRs) and WRs on planar images were conventionally computed. We investigated correlations between planar HMRs and SPECT-CT SUVmeans and between WRs obtained from planar and SPECT-CT images. The cutoff for SPECT-CT WRs defined by linear regression and that of normal planar WRs derived from a database were compared with neurological diagnoses of the patients. We assigned the patients to groups according to clinical diagnoses as controls (n = 6), multiple system atrophy (MSA, n = 7), progressive supranuclear palsy (PSP, n = 17), and Parkinson’s disease or dementia with Lewy bodies (PD/DLB, n = 19), then compared SPECT-CT and planar image parameters.ResultsWe found significant correlations between SPECT-CT SUVmean and planar HMR on early and delayed images (R2 = 0.69 and 0.82, p < 0.0001) and between SPECT-CT and planar WRs (R2 = 0.79, p < 0.0001). A threshold of 31% for SPECT-CT WR based on linear regression resulted in agreement between planar and SPECT-CT WR in 67 (93.1%) of 72 patients. Compared with controls, early and delayed SUVmean in patients with PSP and MSA tended more towards significance than planar HMR. This trend was similar for SPECT-CT WRs in patients with PSP.ConclusionsAbsolute heart counts and SUVmean determined using [123I]MIBG SPECT-CT correlated with findings of conventional planar images in patients with neurological diseases. Three-dimensional quantitation with [123I]MIBG SPECT-CT imaging might differentiate patients with PSP and MSA from controls.

Incidental Extracardiac Findings of Technetium-99m Pyrophosphate Scintigraphy: A Pictorial Review.

Technetium-99m pyrophosphate (Tc-99m PYP) cardiac imaging is a simple, widely available, noninvasive method to identify patients with transthyretin-type cardiac amyloidosis (ATTR),and it has remarkably high diagnostic accuracy with very high sensitivity and specificity. Visual scores of 0, 1, 2, and 3 indicate non-myocardial uptake, uptake less than rib, equal to rib, and greater than rib uptake, respectively. Semiquantitative assessment using the heart-to-contralateral lung ratio of more than 1.5 at 1 hour accurately distinguishes ATTR from the cardiac amyloid light chain subtype. However, there are several incidental non-cardiac findings that can be seen in planar images, rotating single-photon emission computed tomography (SPECT) images, maximum intensity projection images, or computed tomography images acquired for attenuation correction. These findings may lead to the early detection of a noncardiac condition that may require additional treatment. The intent of this review is to demonstrate several incidental noncardiac abnormalities that have an impact on patient management and follow-up.

Bacterial imaging in tumour diagnosis.

Some bacteria, such as Escherichia coli (E. coli) and Salmonella typhimurium (S. typhimurium), have an inherent ability to locate solid tumours, making them a versatile platform that can be combined with other tools to improve the tumour diagnosis and treatment. In anti-cancer therapy, bacteria function by carrying drugs directly or expressing exogenous therapeutic genes. The application of bacterial imaging in tumour diagnosis, a novel and promising research area, can indeed provide dynamic and real-time monitoring in both pre-treatment assessment and post-treatment detection. Different imaging techniques, including optical technology, acoustic imaging, magnetic resonance imaging (MRI) and nuclear medicine imaging, allow us to observe and track tumour-associated bacteria. Optical imaging, including bioluminescence and fluorescence, provides high-sensitivity and high-resolution imaging. Acoustic imaging is a real-time and non-invasive imaging technique with good penetration depth and spatial resolution. MRI provides high spatial resolution and radiation-free imaging. Nuclear medicine imaging, including positron emission tomography (PET) and single photon emission computed tomography (SPECT) can provide information on the distribution and dynamics of bacterial population. Moreover, strategies of synthetic biology modification and nanomaterial engineering modification can improve the viability and localization ability of bacteria while maintaining their autonomy and vitality, thus aiding the visualization of gut bacteria. However, there are some challenges, such as the relatively low bacterial abundance and heterogeneously distribution within the tumour, the high dimensionality of spatial datasets and the limitations of imaging labeling tools. In summary, with the continuous development of imaging technology and nanotechnology, it is expected to further make in-depth study on tumour-associated bacteria and develop new bacterial imaging methods for tumour diagnosis.

Towards Clinical Development of Scandium Radioisotope Complexes for Use in Nuclear Medicine: Encouraging Prospects with the Chelator 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid (DOTA) and Its Analogues.

Scandium (Sc) isotopes have recently attracted significant attention in the search for new radionuclides with potential uses in personalized medicine, especially in the treatment of specific cancer patient categories. In particular, Sc-43 and Sc-44, as positron emitters with a satisfactory half-life (3.9 and 4.0 h, respectively), are ideal for cancer diagnosis via Positron Emission Tomography (PET). On the other hand, Sc-47, as an emitter of beta particles and low gamma radiation, may be used as a therapeutic radionuclide, which also allows Single-Photon Emission Computed Tomography (SPECT) imaging. As these scandium isotopes follow the same biological pathway and chemical reactivity, they appear to fit perfectly into the "theranostic pair" concept. A step-by-step description, initiating from the moment of scandium isotope production and leading up to their preclinical and clinical trial applications, is presented. Recent developments related to the nuclear reactions selected and employed to produce the radionuclides Sc-43, Sc-44, and Sc-47, the chemical processing of these isotopes and the main target recovery methods are also included. Furthermore, the radiolabeling of the leading chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and its structural analogues with scandium is also discussed and the advantages and disadvantages of scandium complexation are evaluated. Finally, a review of the preclinical studies and clinical trials involving scandium, as well as future challenges for its clinical uses and applications, are presented.

Analysis of the performance of PET/CT using 18F-fluorodeoxyglucose in comparison with other diagnostic methods in drug-resistant epilepsy in children

Background. Epilepsy is one of the most common neurological diseases characterized by a persistent predisposition to epileptic seizures and the neurobiological, cognitive, psychological, and social consequences. In recent decades, despite the continuous development of antiepileptic drugs, there are still many patients with epilepsy that progresses to drug-resistant epilepsy. Currently, surgical treatment is one of the most important ways to treat such epilepsy. Collaboration between multidisciplinary teams and the combination of multiple neuroimaging methods are key to determining the exact localization of the epileptogenic zone. New diagnostic methods are being developed and the number of indications for their use is growing. The purpose of the study was to analyze the scientific literature on the effectiveness of positron emission tomography combined with computed tomography (PET/CT) using 18F-fluorodeoxyglucose compared to other diagnostic methods in drug-resistant epilepsy in children. Materials and methods. A literature search using keywords was conducted in Web of Science, Scopus, PubMed, and Elsevier databases. Results. Surgical treatment of drug-resistant epilepsy in children has become a specialized area in neurosurgery. Surgical removal or disconnection of a part of the brain, in which the epileptogenic zone is suspected, allows for a complete cure or a significant reduction in seizure frequency. It has been shown that a prerequisite for postoperative success is the accurate determination of the epileptogenic zone during a multistage preoperative diagnosis. Among many studies, nuclear medicine technologies play an important role in the presurgical examination of children with drug-resistant epilepsy. In combination with other methods, nuclear medicine helps identify the epileptogenic zone, especially in case of conflicting data, negative magnetic resonance imaging — negative epilepsy, focal cortical dysplasia or extratemporal lobe epilepsy. Single-photon emission CT and PET using functional neuroimaging with nuclear medicine indicators are classical methods and are recommended by neuroimaging specialists. In addition, one of the leading modern methods is PET/CT with 18F-fluorodeoxyglucose. It provides information that might be missed when using anatomical methods such as magnetic resonance imaging, and the area of hypometabolism detected with 18F-fluorodeoxyglucose PET/CT may be larger than the area of anatomical lesion detected on magnetic resonance imaging. Conclusions. For children with drug-resistant epilepsy, PET/CT using 18F-fluorodeoxyglucose is the most optimal method of preoperative diagnosis.

Diagnosis and Management of Pediatric Neuropsychiatric Systemic Lupus Erythematosus: An Update.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a potentially serious and life-threatening complication of SLE. The presentation and severity of neuropsychiatric involvement in SLE may show considerable variability. The disease can affect the neural tissue directly or may be associated with vascular involvement, mainly associated with anti-phospholipid (aPL) antibodies. A direct causal link with SLE may sometimes be challenging since there are many confounding factors and the symptoms may be non-specific. Despite its remarkable sensitivity in detecting hemorrhagic and ischemic stroke, transverse myelitis and ischemic infarction, magnetic resonance imaging (MRI) lacks the spatial resolution required to identify microvascular involvement. When standard MRI fails to detect a suspicious lesion, it is advisable to use advanced imaging modalities such as positron emission tomography (PET), single photon emission computed tomography (SPECT) or quantitative MRI, if available. Even with these advanced modalities, the specificity of neuroimaging in NPSLE remains inadequate (60-82% for MRI). Neuropsychiatric syndromes, such as cerebrovascular events, seizures and cognitive impairments appear to be associated with serum aPL antibodies. Some studies have shown that anti-ribosomal P antibodies have a low sensitivity for NPSLE and a limited contribution to the differentiation of different clinical entities. Treatment has two main goals: symptomatic relief and treatment of the disease itself. Commonly used immunosuppressants for NPSLE include cyclophosphamide (CYC), azathioprine (AZA), and mycophenolate mofetil (MMF). According to EULAR's current recommendation, strong immunosuppressants such as CYC and rituximab (RTX) should be preferred. Biologics have also been used in NPSLE. Fingolimod, eculizumab, and JAK inhibitors are potential drugs in the pipeline. Developing targeted therapies will be possible by a better understanding of the pathological mechanisms.

Utility of combining multiple parameters of 123I-IMP SPECT and voxel-based morphometry MRI using a multiparametric scoring system for differentiating dementia with Lewy bodies from Alzheimer's disease.

Brain magnetic resonance imaging voxel-based morphometry (VBM) and perfusion single-photon emission computed tomography (SPECT) are useful for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). To determine whether combining multiple parameters of VBM and SPECT using a multiparametric scoring system (MSS) improves diagnostic accuracy in differentiating DLB from AD. In total, 23 patients with DLB and 57 patients with AD underwent imaging using a voxel-based specific regional analysis system for AD (VSRAD), an easy Z-score imaging system, and a Z-Graph using three-dimensional stereotactic surface projection. The cutoff values were determined using the receiver operating characteristic curve to differentiate DLB from AD for all parameters. Patients were scored 1 (DLB) or 0 (AD) for each statistically significant parameter, according to a threshold. The total score was determined for each case to obtain a cutoff value for the MSS. The mean Z-scores in the medial temporal lobes using the VSRAD were significantly lower in patients with DLB than in those with AD. Each Z-score of the summed Z-scores in all four segmented regions of the occipital lobes using the Z-Graph was significantly higher in patients with DLB than in those with AD. Among the five parameters, the highest accuracy was 80% for the Z-score of the summed Z-scores in the left medial occipital lobe. For the MSS, a cutoff value of four improved the diagnostic accuracy to 82%. MSS was more accurate than any single parameter of VBM or SPECT in differentiating DLB from AD.

Quantitative Bone SPECT/CT of Central Cartilaginous Bone Tumors: Relationship between SUVmax and Radiodensity in Hounsfield Unit.

(1) Background: it is challenging to determine the accurate grades of cartilaginous bone tumors. Using bone single photon emission computed tomography (SPECT)/computed tomography (CT), maximum standardized uptake value (SUVmax) was found to be significantly associated with different grades of cartilaginous bone tumor. The inquiry focused on the effect of the tumor matrix on SUVmax. (2) Methods: a total of 65 patients from 2017 to 2022 with central cartilaginous bone tumors, including enchondromas and low-to-intermediate grade chondrosarcomas, who had undergone bone SPECT/CT were retrospectively enrolled. The SUVmax was recorded and any aggressive CT findings of cartilaginous bone tumor and Hounsfield units (HU) of the chondroid matrix as mean, minimum, maximum, and standard deviation (SD) were reviewed on CT scans. Pearson's correlation analysis was performed to determine the relationship between CT features and SUVmax. Subgroup analysis was also performed between the benign group (enchondroma) and the malignant group (grade 1 and 2 chondrosarcoma) for comparison of HU values and SUVmax. (3) Results: a significant negative correlation between SUVmax and HU measurements, including HUmax, HUmean, and HUSD, was found. The subgroup analysis showed significantly higher SUVmax in the malignant group, with more frequent CT aggressive features, and significantly lower HUSD in the malignant group than in the benign group. (4) Conclusions: it was observed that higher SUVmax and lower HUSD were associated with a higher probability of having a low-to-intermediate chondrosarcoma with aggressive features and a less calcified tumor matrix.

Enhancing voxel-based dosimetry accuracy with an unsupervised deep learning approach for hybrid medical image registration.

Deformable registration is required to generate a time-integrated activity (TIA) map which is essential for voxel-based dosimetry. The conventional iterative registration algorithm using anatomical images (e.g., computed tomography (CT)) could result in registration errors in functional images (e.g., single photon emission computed tomography (SPECT) or positron emission tomography (PET)). Various deep learning-based registration tools have been proposed, but studies specifically focused on the registration of serial hybrid images were not found. In this study, we introduce CoRX-NET, a novel unsupervised deep learning network designed for deformable registration of hybrid medical images. The CoRX-NET structure is based on the Swin-transformer (ST), allowing for the representation of complex spatial connections in images. Its self-attention mechanism aids in the effective exchange and integration of information across diverse image regions. To augment the amalgamation of SPECT and CT features, cross-stitch layers have been integrated into the network. Two different 177 Lu DOTATATE SPECT/CT datasets were acquired at different medical centers. 22 sets from Seoul National University and 14 sets from Sunway Medical Centre are used for training/internal validation and external validation respectively. The CoRX-NET architecture builds upon the ST, enabling the modeling of intricate spatial relationships within images. To further enhance the fusion of SPECT and CT features, cross-stitch layers have been incorporated within the network. The network takes a pair of SPECT/CT images (e.g., fixed and moving images) and generates a deformed SPECT/CT image. The performance of the network was compared with Elastix and TransMorph using L1 loss and structural similarity index measure (SSIM) of CT, SSIM of normalized SPECT, and local normalized cross correlation (LNCC) of SPECT as metrics. The voxel-wise root mean square errors (RMSE) of TIA were compared among the different methods. The ablation study revealed that cross-stitch layers improved SPECT/CT registration performance. The cross-stitch layers notably enhance SSIM (internal validation: 0.9614vs. 0.9653, external validation: 0.9159vs. 0.9189) and LNCC of normalized SPECT images (internal validation: 0.7512vs. 0.7670, external validation: 0.8027vs. 0.8027). CoRX-NET with the cross-stitch layer achieved superior performance metrics compared to Elastix and TransMorph, except for CT SSIM in the external dataset. When qualitatively analyzed for both internal and external validation cases, CoRX-NET consistently demonstrated superior SPECT registration results. In addition, CoRX-NET accomplished SPECT/CT image registration in less than 6s, whereas Elastix required approximately 50s using the same PC's CPU. When employing CoRX-NET, it was observed that the voxel-wise RMSE values for TIA were approximately 27% lower for the kidney and 33% lower for the tumor, compared to when Elastix was used. This study represents a major advancement in achieving precise SPECT/CT registration using an unsupervised deep learning network. It outperforms conventional methods like Elastix and TransMorph, reducing uncertainties in TIA maps for more accurate dose assessments.

Hyperbaric oxygen therapy vs. pharmacological intervention in adults with fibromyalgia related to childhood sexual abuse: prospective, randomized clinical trial

Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by disruptions in pain processing within the central nervous system. It exhibits a high prevalence among patients with a history of traumatic experiences, notably childhood sexual abuse (CSA). This study compared the efficacy of hyperbaric oxygen therapy (HBOT) to the current pharmacological standard of care for individuals suffering from CSA-related FMS. Forty-eight participants diagnosed with FMS and a history of CSA were randomly assigned to either the HBOT group (60 sessions of 100% oxygen at 2 ATA for 90 min, with air breaks every 5 min) or the medication (MED) group (FDA-approved medications, Pregabalin and Duloxetine). The primary endpoint was the Fibromyalgia impact questionnaire (FIQ) score, while secondary endpoints encompassed emotional status and daily functioning questionnaires, as well as pain thresholds and conditioned pain modulation tests. Brain activity was evaluated through single photon emission computed tomography (SPECT). Results revealed a significant group-by-time interaction for the FIQ score favoring HBOT over MED (p < 0.001), with a large effect size (Cohen's d = − 1.27). Similar findings were observed in emotional symptoms and functional measures. SPECT imaging demonstrated an increase in activity in pre-frontal and temporal brain areas, which correlated with symptoms improvement. In conclusion, HBOT exhibited superior benefits over medications in terms of physical, functional, and emotional improvements among FMS patients with a history of CSA. This associated with increased activity in pre-frontal and temporal brain areas, highlighting the neuroplasticity effect of HBOT.

Efficacy of a Novel Respiratory Motion Reduction Block in Reducing Motion Artifact on Myocardial Perfusion Single-Photon Emission Computed Tomography.

Motion artifacts caused by heart motion during myocardial perfusion single-photon emission computed tomography (SPECT) can compromise image quality and diagnostic accuracy. This study aimed to evaluate the efficacy of the novel respiratory motion reduction block (RRB) device in reducing motion artifacts by compressing the hypochondrium and improving SPECT image quality. In total, 91 patients who underwent myocardial perfusion SPECT with 99mTc-sestamibi were retrospectively analyzed. Patients (n = 28) who underwent SPECT without the RRB were included in the control group, and those (n = 63) who underwent SPECT with the RRB were in the RRB group. The distance of heart motion during dynamic acquisition was measured, and projection data were assessed for patient motion and motion artifacts. Patient motion was classified into various levels, and motion artifacts on SPECT images were visually examined. The distances of heart motion without and with the RRB were 15.4 ± 5.3 and 7.5 ± 2.3, respectively. Compared with the control group, the RRB group had a lower frequency of heart motion based on the projection data, particularly in terms of creep and shift motion. The RRB group had a significantly lower incidence of motion artifacts on SPECT images than the control group. The RRB substantially reduced specific types of motion, such as shift and creep, and had a low influence on bounce motion. However, it could effectively suppress respiratory-induced heart motion and reduce motion artifacts on myocardial perfusion SPECT, thereby emphasizing its potential for improving image quality.

Indium-111 radiolabelling of a brain-penetrant Aβ antibody for SPECT imaging.

The development of bispecific antibodies that can traverse the blood-brain barrier has paved the way for brain-directed immunotherapy and when radiolabelled, immunoPET imaging. The objective of this study was to investigate how indium-111 (111In) radiolabelling with compatible chelators affects the brain delivery and peripheral biodistribution of the bispecific antibody RmAb158-scFv8D3, which binds to amyloid-beta (Aβ) and the transferrin receptor (TfR), in Aβ pathology-expressing tg-ArcSwe mice and aged-matched wild-type control mice. Bispecific RmAb158-scFv8D3 (biAb) was radiolabelled with 111In using CHX-A"-DTPA, DOTA, or DOTA-tetrazine (DOTA-Tz). Affinity toward TfR and Aβ, as well as stability, was investigated in vitro. Mice were then intravenously administered with the three different radiolabelled biAb variants, and blood samples were collected for monitoring pharmacokinetics. Brain concentration was quantified after 2 and 72 h, and organ-specific retention was measured at 72 h by gamma counting. A subset of mice also underwent whole-body Single-photon emission computed tomography (SPECT) scanning at 72 h after injection. Following post-mortem isolation, the brains of tg-ArcSwe and WT mice were sectioned, and the spatial distribution of biAb was further investigated with autoradiography. All three [111In]biAb variants displayed similar blood pharmacokinetics and brain uptake at 2 h after administration. Radiolabelling did not compromise affinity, and all variants showed good stability, especially the DOTA-Tz variant. Whole-body SPECT scanning indicated high liver, spleen, and bone accumulation of all [111In]biAb variants. Subsequent ex vivo measurement of organ retention confirmed SPECT data, with retention in the spleen, liver, and bone - with very high bone marrow retention. Ex vivo gamma measurement of brain tissue, isolated at 72 h post-injection, and ex vivo autoradiography showed that WT mice, despite the absence of Aβ, exhibited comparable brain concentrations of [111In]biAb as those found in the tg-ArcSwe brain. The successful 111In-labelling of biAb with retained binding to TfR and Aβ, and retained ability to enter the brain, demonstrated that 111In can be used to generate radioligands for brain imaging. A high degree of [111In]biAb in bone marrow and intracellular accumulation in brain tissue indicated some off-target interactions or potential interaction with intrabrain TfR resulting in a relatively high non-specific background signal.

Prostate-Specific Membrane Antigen Targeted StarPEG Nanocarrier for Imaging and Therapy of Prostate Cancer.

The tumor uptake of large non-targeted nanocarriers primarily occurs through passive extravasation, known as the enhanced permeability and retention (EPR) effect. Prior studies demonstrated improved tumor uptake and retention of 4-arm 40 kDa star polyethylene glycol (StarPEG) polymers for cancer imaging by adding prostate-specific membrane antigen (PSMA) targeting small molecule ligands. To test PSMA-targeted delivery and therapeutic efficacy, StarPEG nanodrugs with/without three copies of PSMA-targeting ligands, ACUPA, are designed and synthesized. For single-photon emission computed tomography (SPECT) imaging and therapy, each nanocarrier is labeled with 177Lu using DOTA radiometal chelator. The radiolabeled nanodrugs, [177Lu]PEG-(DOTA)1 and [177Lu]PEG-(DOTA)1(ACUPA)3, are evaluated in vitro and in vivo using PSMA+ PC3-Pip and/or PSMA- PC3-Flu cell lines, subcutaneous xenografts and disseminated metastatic models. The nanocarriers are efficiently radiolabeled with 177Lu with molar activities 10.8-15.8 MBq/nmol. Besides excellent in vitro PSMA binding affinity (kD = 51.7nM), the targeted nanocarrier, [177Lu]PEG-(DOTA)1(ACUPA)3, demonstrated excellent in vivo SPECT imaging contrast with 21.3% ID/g PC3-Pip tumors uptake at 192h. Single doses of 18.5MBq [177Lu]PEG-(DOTA)1(ACUPA)3 showed complete resolution of the PC3-Pip xenografts observed up to 138days. Along with PSMA-targeted excellent imaging contrast, these results demonstrated high treatment efficacy of [177Lu]PEG-(DOTA)1(ACUPA)3 for prostate cancer, with potential for clinical translation.

Preclinical evaluation of MC1R targeting theranostic pair [155Tb]Tb-crown-αMSH and [161Tb]Tb-crown-αMSH

BackgroundTargeted radionuclide therapy is established as a highly effective strategy for the treatment of metastatic tumors; however, the co-development of suitable imaging companions to therapy remains significant challenge. Theranostic isotopes of terbium (149Tb, 152Tb, 155Tb, 161Tb) have the potential to provide chemically identical radionuclidic pairs, which collectively encompass all modes of nuclear decay relevant to nuclear medicine. Herein, we report the first radiochemistry and preclinical studies involving 155Tb- and 161Tb-labeled crown-αMSH, a small peptide-based bioconjugate suitable for targeting melanoma. Methods155Tb was produced via proton induced spallation of Ta targets using the isotope separation and acceleration facility at TRIUMF with isotope separation on-line (ISAC/ISOL). The radiolabeling characteristics of crown-αMSH with 155Tb and/or 161Tb were evaluated by concentration-dependence radiolabeling studies, and radio-HPLC stability studies. LogD7.4 measurements were obtained for [161Tb]Tb-crown-αMSH. Competitive binding assays were undertaken to determine the inhibition constant for [natTb]Tb-crown-αMSH in B16-F10 cells. Pre-clinical biodistribution and SPECT/CT imaging studies of 155Tb and 161Tb labeled crown-αMSH were undertaken in male C57Bl/6 J mice bearing B16-F10 melanoma tumors to evaluate tumor specific uptake and imaging potential for each radionuclide. ResultsQuantitative radiolabeling of crown-αMSH with [155Tb]Tb3+ and [161Tb]Tb3+ was demonstrated under mild conditions (RT, 10 min) and low chelator concentrations; achieving high molar activities (23–29 MBq/nmol). Radio-HPLC studies showed [161Tb]Tb-crown-αMSH maintains excellent radiochemical purity in human serum, while gradual metabolic degradation is observed in mouse serum. Competitive binding assays showed the high affinity of [natTb]Tb-crown-αMSH toward MC1R. Two different methods for preparation of the [155Tb]Tb-crown-αMSH radiotracer were investigated and the impacts on the biodistribution profile in tumor bearing mice is compared. Preclinical in vivo studies of 155Tb- and 161Tb- labeled crown-αMSH were performed in parallel, in mice bearing B16-F10 tumors; where the biodistribution results showed similar tumor specific uptake (6.06–7.44 %IA/g at 2 h pi) and very low uptake in nontarget organs. These results were further corroborated through a series of single-photon emission computed tomography (SPECT) studies, with [155Tb]Tb-crown-αMSH and [161Tb]Tb-crown-αMSH showing comparable uptake profiles and excellent image contrast. ConclusionsCollectively, our studies highlight the promising characteristics of [155Tb]Tb-crown-αMSH and [161Tb]Tb-crown-αMSH as theranostic pair for nuclear imaging (155Tb) and radionuclide therapy (161Tb).

Late Outcomes of Undiagnosed Unilateral Condylar Hyperplasia and Reoccurrence of Mandibular Asymmetry.

Unilateral condylar hyperplasia (UCH) is a rare cause of asymmetrical mandibular overgrowth because of the presence of an atypical growth in the affected condyle. SPECT (single-photon emission computed tomography) can easily establish the presence of an atypical, prolonged growth exceeding far beyond normal condylar growth and activity. A CT, CBCT, or LDCT (computed tomography, cone-beam computed tomography, or low-dose computed tomography) can confirm the diagnosis by evaluating the scope of bone overgrowth, mandibular basis/ramus asymmetry, tendency to condylar head enlargement, changes in bone density, and occurrence of differences in condylar head shapes, size, and bone structure. In most cases, a condylectomy is the procedure of choice in growing cases of UCH to remove the pathological condyle and reduce asymmetry levels. Sometimes, the growth is very slow and progressive over time, causing slowly growing asymmetry with similar symptoms to any other mandibular asymmetry, and this causes some troublesome procedures in UCH diagnostics, resulting in patients being underdiagnosed; it can even lead to some relapses in mandibular asymmetry and skeletal malocclusion after previously performed orthodontic and surgical treatment of such discrepancies. When the source of asymmetry is not identified in time, possible inadequate treatment protocols can be used. If any relapse of facial and mandibular asymmetry re-occur, SPECT and CT evaluation are necessary to evaluate if condylar hyperplasia is present and to establish what kind of surgical intervention should be used in each case.