Single Photon Emission Computed Tomography Research Articles

Improvement of Basal Ganglia Detectability in Brain Single Photon Emission Computerized Tomography by Wavelet Transformation in Image Processing Domain: A XCAT Phantom Study

Purpose: Noise in brain Single Photon Emission Computed Tomography (SPECT) images limits an early diagnosis of Parkinson's Disease (PD). To overcome the limitation, as an image processing approach, wavelet transformation was used to denoising the images also with a segmentation method to differentiate the basal ganglia in brain SPECT.
 Materials and Methods: The brain scans of the human 4D Extended Cardiac Torso (XCAT) phantom through the Simulating Medical Imaging Nuclear Detectors (SIMIND) simulated SPECT system were imported to the MATLAB toolkit for image processing. The reconstructed brain images by iterative reconstruction were de-noised through 9 methods of wavelet transformation at different levels, and then six segmentation methods were applied to differentiate the caudate and putamen. The Dice coefficient, Specificity, and Sensitivity evaluation criteria were calculated based on the adaptive thresholding of the selected images from segmentation. A ground truth image was manually marked by a clinical nuclear medicine specialist.
 Results: The dice coefficient was obtained in a range from 0.3979 to 0.6299, as well as the specificity criterion from 0.7682 to 0.8168 and the sensitivity from 0.9049 to 0.9871.
 The results from adaptive threshold segmentation and the evaluation criteria showed that the best levels of the nucleuses detectability were provided by level 7 of Biorthogonal, levels 4 and 7 of Coiflet, level 6 of Daubechies, level 5 of Haar, level 6 of Morlet and level 6 of Symlet methods.
 Conclusion: Parkinson’s disease may be diagnosed in the early stage by an image processing approach to improve the quality of brain SPECT images.

Relationship between transient ischemic dilatation and changes in heart rate during gated SPECT acquisition in a low-risk population without perfusion defects.

Transient ischemic dilatation (TID) in myocardial perfusion single photon emission computed tomography (SPECT) is considered a marker of poor prognosis. However, it has been suggested that some cases are due to apparent volumetric changes secondary to differences in heart rate (HR) at the time of acquisition. We assessed the correlation between transient dilatation and HR in low risk patients with no perfusion defects. We retrospectively analyzed patients sent for 99mTc-MIBI SPECT using a 2-day protocol. We recorded the median HR during acquisition and the HR difference (HRD) between the rest and post-stress. We obtained the medium ventricular volume, end-diastolic volume (EDV), and end-systolic volume (ESV). We included patients in which TID using medium ventricular volume (TIDMV) was ≥1.2. TID was also calculated for the EDV and ESV (TIDEDV, TIDESV). We excluded patients with known coronary artery disease, perfusion defects, various ECG disorders, positive stress test, or ESV < 10 ml. From a total of 2006 patients, 63 (50 exercise, 13 dipyridamole) met the criteria for analysis (age 63.8 ± 9.7, 44 men). TIDMV was 1.29 ± 0.09 and HRD 9.8 beats per minute (BPM) (range -10 to 41). There was positive correlation between HRD and TIDMV ( r  = 0.51, P  < 0.001) and TIDEDV ( r  = 0.5, P  < 0.001), but not TIDESV ( r  = 0.23, P  = 0.07). Correlation was stronger when HRD was ≥10 BPM ( r  = 0.67, P  < 0.001). TID without perfusion defects should be interpreted with caution in the presence of HRD ≥ 10 BPM during post-stress acquisition.

Assessment of SPECT Image Reconstruction in Liver Scanning Using 99mTc/ EDDA/ HYNIC-TOCAssessment of SPECT Image Reconstruction in Liver Scanning Using 99mTc/ EDDA/ HYNIC-TOC

Purpose: Given that the Single Photon Emission Computed Tomography (SPECT) image quality is defined experimentally, developing a specialized scanning technique for each procedure is necessary to increase the diagnosis accuracy. This study aims to determine the optimal algorithm for liver scan reconstruction using 99mTc/SPECT.&#x0D; Materials and Methods: The Filtered Back-Projection (FBP) reconstruction method was used in liver scanning using 99mTc-EDDA/HYNIC-TOC (Tektrotyd) for SPECT images of 30 patients which were acquired with a dual-head EvoExel detector system. Using different types of filters in SPECT imaging, various optimal results can be achieved in the processed images, such as artifact reduction, noise reduction, or signal enhancement and recovery. To evaluate the effect of different filters on image quality, Signal-to-Noise-Ratio (SNR), Contrast-to-Noise-Ratio (CNR), and contrast parameters were calculated.&#x0D; Results: Applying filters enhanced contrast in the images in most cases as well as CNR and SNR. Metz (power = 2), Shepp-Logan (Cut-off frequency = 0.67) and Metz (power = 2) filters increase the CNR, contrast and SNR in images more than the other filters, respectively. The maximum improvement for CNR, contrast and SNR was from 0.62 to 2.35, 0.99 to 1.31, and 8.48 to 14.70, respectively.&#x0D; Conclusion: Based on the results, the Hamming filter, due to providing high-quality images for visual analysis of liver SPECT, and the Butterworth filter, due to balancing the image quality and noise for quantitative analysis, are recommended.

Synthesis, Screening, and Evaluation of Theranostic Molecular CPCR4-Based Probe Targeting CXCR4.

Chemokines and chemokine receptors are indispensable to play a key role in the development of malignant tumors. As one of the most widely expressed chemokine receptors, chemokine (C-X-C motif) receptor 4 (CXCR4) has been a popular research focus. In most tumors, CXCR4 expression is significantly upregulated. Moreover, integrated nuclide diagnosis and therapy targeting CXCR4 show great potential. [68Ga]Ga-pentixafor, a radioligand targeting CXCR4, exhibits a strong affinity for CXCR4 both in vivo and in vitro. However, [177Lu]Lu-pentixather, the therapeutic companion of [68Ga]Ga-pentixafor, requires significant refinement to mitigate its pronounced hepatic biodistribution. The objective of this study was to synthesize theranostic molecular tracers with superior CXCR4 targeting functions. The Daudi cell line, which highly expressed CXCR4, and the MM.1S cell line, which weakly expressed CXCR4, were used in this study. Based on the pharmacophore cyclo (-d-Tyr-n-me-d-Orn-l-Arg-L-2-NAL-Gly-) (CPCR4) of pentixafor, six tracers were synthesized: [124I]I-1 ([124I]I-CPCR4), [99mTc]Tc-2 ([99mTc]Tc-HYNIC-CPCR4), [124I]I-3 ([124I]I-pentixafor), [18F]AlF-4 ([18F]AlF-NETA-CPCR4), [99mTc]Tc-5 ([99mTc]Tc-MAG3-CPCR4) and [124I]I-6 ([124I]I-pentixafor-Ga) and their radiochemical purities were all higher than 95%. After positron emission tomography (PET)/single-photon emission computed tomography (SPECT) imaging, the [124I]I-6 group exhibited the best target-nontarget ratio. At the same time, comparing the [68Ga]Ga-pentixafor group with the [124I]I-6 group, we found that the [124I]I-6 group had a better target-nontarget ratio and lower uptake in nontarget organs. Therefore, compound 6 was selected for therapeutic radionuclide (131I) labeling, and the tumor-bearing animal models were treated with [131I]I-6. The volume of the tumor site was significantly reduced in the treatment group compared with the control group, and no significant side effects were found. [124I]I-6 and [131I]I-6 showed excellent affinity for targeting CXCR4, and they showed great potential for the integrated diagnosis and treatment of tumors with high CXCR4 expression.

A Survey on AI-based Parkinson Disease Detection: Taxonomy, Case Study, and Research Challenges

Parkinson Disease (PD) is most common diseases from majority of disease encountered all over the world, with more than 7 million individuals being affected. PD is a type of progressive nervous system disease, causing deterioration in health or function. The timely identification of PD is a significant challenge because it rarely shows symptoms in the early stages. Moreover, it is typically encountered in older people where the symptoms sometimes coincide with age-related issues. Deep Learning (DL) can be integrated into many methodologies in diagnosing PD, such as Magnetic Resonance Imaging (MRI) and Single-Photon Emission Computed Tomography (SPECT). DL algorithms can detect PD based on observing some common symptoms. Moreover, it can also be detected using brain MRI images. So, in this study, we reviewed existing DL algorithms for timely identification of PD. We also have developed a CNN model for the timely identification of PD. We used 3D brain MRI images of PPMI datasets and achieved the 88% accuracy.  

Status and Development of Nuclear Medicine Over One Decade in Beijing

Abstract Objective Our objective was to investigate the basic information of the personnel and facilities of nuclear medicine in Beijing. Methods This survey was performed by the Beijing Quality Control Center in 2018. The investigation included personnel, equipment, and clinical applications, and data were then compared with previous surveys. The paper questionnaires were used for the survey, which required information about the personnel, devices, and clinical applications. Results About 38 nuclear medicine departments in Beijing were involved in the survey. The number of nuclear medicine staff was 531 in 2018, showing an increase of 58.7% over the past decade. Positron emission tomography/computed tomography (PET/CT), single-photon emission computed tomography (SPECT), and single-photon emission computed tomography/computed tomography (SPECT/CT) represented the main nuclear medicine facilities, and the total number of surveyed departments was 18, 24, and 34, respectively. The quality control results showed significant improvement from the 2005 levels. The total number of scintigraphy procedures was estimated at 199,607 (153,185 SPECT and 46,422 PET/CT). The estimated annual number of scintigraphy images was 8.9 per 1,000 population for SPECT and 2.7 per 1,000 population for PET/CT during 2018. The most frequent radioiodine-targeted therapy was 131I-targeted therapy for hyperthyroidism in 2018. Conclusions Nuclear medicine has experienced rapid growth in the past 10 years in Beijing, either in personnel, equipment, and scintigraphy. Future efforts will focus on the use of new isotopes in the diagnosis, implementing quality strategy, and enhancing training.

Robustness of radiomic features in 123I-ioflupane-dopamine transporter single-photon emission computer tomography scan.

Radiomic features are usually used to predict target variables such as the absence or presence of a disease, treatment response, or time to symptom progression. One of the potential clinical applications is in patients with Parkinson's disease. Robust radiomic features for this specific imaging method have not yet been identified, which is necessary for proper feature selection. Thus, we are assessing the robustness of radiomic features in dopamine transporter imaging (DaT). For this study, we made an anthropomorphic head phantom with tissue heterogeneity using a personal 3D printer (polylactide 82% infill); the bone was subsequently reproduced with plaster. A surgical cotton ball with radiotracer (123I-ioflupane) was inserted. Scans were performed on the two-detector hybrid camera with acquisition parameters corresponding to international guidelines for DaT single photon emission tomography (SPECT). Reconstruction of SPECT was performed on a clinical workstation with iterative algorithms. Open-source LifeX software was used to extract 134 radiomic features. Statistical analysis was made in RStudio using the intraclass correlation coefficient (ICC) and coefficient of variation (COV). Overall, radiomic features in different reconstruction parameters showed a moderate reproducibility rate (ICC = 0.636, p <0.01). Assessment of ICC and COV within CT attenuation correction (CTAC) and non-attenuation correction (NAC) groups and within particular feature classes showed an excellent reproducibility rate (ICC > 0.9, p < 0.01), except for an intensity-based NAC group, where radiomic features showed a good repeatability rate (ICC = 0.893, p <0.01). By our results, CTAC becomes the main threat to feature stability. However, many radiomic features were sensitive to the selected reconstruction algorithm irrespectively to the attenuation correction. Radiomic features extracted from DaT-SPECT showed moderate to excellent reproducibility rates. These results make them suitable for clinical practice and human studies, but awareness of feature selection should be held, as some radiomic features are more robust than others.

Preparation, Biological Evaluation, and First-in-Human Single-Photon Emission Computed Tomography (SPECT) Study of 99mTc-Labeled Prostate-Specific Membrane Antigen (PSMA)-Targeted Radiotracers Containing Triazole with Reduced Kidneys Accumulation

Preparation, Biological Evaluation, and First-in-Human Single-Photon Emission Computed Tomography (SPECT) Study of ^99mTc-Labeled Prostate-Specific Membrane Antigen (PSMA)-Targeted Radiotracers Containing Triazole with Reduced Kidneys Accumulation

Influence of Body Mass Index on Radiation Exposure Across Imaging Modalities in the Evaluation of Chest Pain.

Essential to a patient-centered approach to imaging individuals with chest pain is knowledge of differences in radiation effective dose across imaging modalities. Body mass index (BMI) is an important and underappreciated predictor of effective dose. This study evaluated the impact of BMI on estimated radiation exposure across imaging modalities. This was a retrospective analysis of patients with concern for cardiac ischemia undergoing positron emission tomography (PET)/computed tomography (CT), cadmium zinc telluride single-photon emission CT (SPECT) myocardial perfusion imaging, or coronary CT angiography (CCTA) using state-of-the-art imaging modalities and optimal radiation-sparing protocols. Radiation exposure was calculated across BMI categories based on established cardiac imaging-specific conversion factors. Among 9046 patients (mean±SD age, 64.3±13.1 years; 55% men; mean±SD BMI, 30.6±6.9 kg/m2), 4787 were imaged with PET/CT, 3092 were imaged with SPECT/CT, and 1167 were imaged with CCTA. Median (interquartile range) radiation effective doses were 4.4 (3.9-4.9) mSv for PET/CT, 4.9 (4.0-6.3) mSv for SPECT/CT, and 6.9 (4.0-11.2) mSv for CCTA. Patients at a BMI <20 kg/m2 had similar radiation effective dose with all 3 imaging modalities, whereas those with BMI ≥20 kg/m2 had the lowest effective dose with PET/CT. Radiation effective dose and variability increased dramatically with CCTA as BMI increased, and was 10 times higher in patients with BMI >45 kg/m2 compared with <20 kg/m2 (median, 26.9 versus 2.6 mSv). After multivariable adjustment, PET/CT offered the lowest effective dose, followed by SPECT/CT, and then CCTA (P<0.001). Although median radiation exposure is modest across state-of-the-art PET/CT, SPECT/CT, and CCTA systems using optimal radiation-sparing protocols, there are significant variations across modalities based on BMI. These data are important for making patient-centered decisions for ischemic testing.

Assessment of arterial blood flow in the microvasculature of the lower extremities in patients with chronic ischemia using a single-photon emission computed tomography (SPECT)

Introduction. Obliterating atherosclerosis of the lower extremity vessels is a chronic, steadily progressive disease of the leg arteries, with a high risk of limb amputation and death. Timely diagnosis and adequate treatment will help slow the disease progression, maintain the patient’s good health for a long time and avoid complications. Purpose. To study arterial blood flow in the microvasculature of the lower extremities, to qualitatively and quantitatively assess perfusion disturbances in functionally significant muscles of the lower extremities. Material and methods. Radionuclide examination of the main vessels and microvasculature of the lower extremities was performed in 36 patients, five of them with a diagnosis of lower extremity obliterating atherosclerosis in dynamics. Radiopharmaceuticals was administered through a catheter installed endovascularly above the aortic bifurcation when patients underwent arteriography of the lower extremity vessels, which also involves intra-arterial administration of a radiopaque contrast agent. Results. When processing the radiological study results, we visually assessed the distribution of radiopharmaceuticals in the vascular bed of the lower extremities, identified the asymmetry in the accumulation of radiopharmaceuticals as a percentage, quantified the accumulation of radiopharmaceutical pulses in the projection of the pelvic, thigh, leg and foot muscles, determining the level of accumulation in each of the areas of interest as a percentage. The radiological study results and direct aortic arteriography of the lower extremities with determination of the level of arterial stenosis confirmed the ischemic nature of the pain syndrome; and in the control study, the effectiveness of treatment with an improvement in perfusion parameters. Conclusions. Intra-arterial administration of radiopharmaceuticals makes it possible to assess the condition of the peripheral arterial bed, which has a significant role in the prognosis of lower extremity atherosclerosis and the results of reconstructive interventions. The method makes possible a hybrid topometric comparison of arterio-perfusion maps for diagnosis, planned treatment and monitoring of its results in dynamics.

Pharmacological test with nitroglycerin in combination with perfusion SPECT with &lt;sup&gt;99m&lt;/sup&gt;Tc-Technetril in assessing the viability of ischemic myocardium in patients after acute infarction

Aim. To evaluate the possibility of using nitroglycerin sublingually in combination with 99mTc-Technetril cardiac perfusion single-photon emission computed tomography (SPECT) as a test for detecting viable myocardium. Material and methods. 28 male patients with coronary heart disease (CHD) and postinfarction cardiosclerosis were examined. Group 1 included 10 patients with CHD without signs of acute myocardial infarction (AMI). Group 2 comprised 18 patients with CHD, postinfarction cardiosclerosis (PICS). The control group consisted of patients who were subsequently rejected a diagnosis of CHD. Patients took 2 tablets (1 mg) of nitroglycerin sublingually, and then, at the peak of the drug’s action (after 3–5 minutes), they were intravenously administered 370 MBq of 99mTc-Technetril (by Diamed, Russia). Myocardial SPECT with 99mTc-Technetril was performed 1 hour after RFP injection. The next day, myocardial SPECT with 99mTc-Technetril was repeated at rest. Results. When taking tableted nitroglycerin at a dose of 1 mg sublingually, its maximum plasma concentration is on average 0.26 ± 0.04 microcgram/l. It is reached by 110–150 s, then maintained within 10 % of the maximum for 7-9 minutes. Nitroglycerin leads to improvement in global and local contractility and increased LV pumping function in CHD patients. This is most pronounced in individuals with a higher class of angina pectoris after AMI and major changes in intracardiac hemodynamics initially. The nitroglycerin test in combination with 99mTc-Technetril SPECT-CT allowed to identify myocardial areas with improved blood flow and increased EFLV after CABG. Conclusion. The nitroglycerin test in combination with 99mTc-Technetril SPECT-CT is effective for detecting viable myocardium in patients with coronary atherosclerosis and CHD, safe and relatively simple due to the sublingual route of nitroglycerin intake.

Clinical and experimental parallels in the assessment of microcirculatory dysfunctions of the lungs in thoracic radiology

Introduction. Chronic obstructive disease (COPD) and thromboembolism of the branches of the pulmonary artery or pulmonary embolism (PE) remain the most common and socially significant lung diseases. Circulatory disorders in these pathologies play a critical role in the development of the disease. Radiation techniques, such as computed tomography/angiography and single-photon emission computed tomography (SPECT), are the leading ones in recognizing changes in the lung parenchyma and vessels. Many questions can be successfully solved experimentally. The main radiation techniques used to study the vascular bed when modeling lung diseases in experimental animals are microangiography and perfusion scintigraphy. Purpose. To show the capabilities of radiation diagnostic methods for identifying vascular disorders in COPD and PE in experiments and clinical manifestations. Material and methods. A clinical and experimental comparison of pulmonary circulation changes during COPD and PE was carried out based on the results of perfusion scintigraphy/SPECT in 55 rats with simulated COPD- like condition and 622 patients with COPD of varying severity, as well as 58 rats with simulated PE and 180 patients with PE. Results. When modelling lung diseases (PE and COPD), the results similar to blood circulation and structural changes in the lung parenchyma in patients with these nosologies were obtained. In COPD, changes in the lung parenchyma correlated with disturbances in functional indicators (microcirculation, PaO2, PaCO2, DSLzd, DLco/VA, SDPA) and increased levels of endothelin-1 (r=0.72) and endothelial growth factor (VEGF-A) (r=0.79). Analysis of experimental and clinical data on PE showed the importance of identifying minor forms of thromboembolism. Conclusion. 1. Persistent microcirculatory dysfunctions in the pulmonary circulation play an important role in the pathogenesis of chronic broncho-obstructive pathology. After just 7 days, initial signs of emphysema can be detected in the ischemic area of the lung tissue, and by the 60th day typical bullous cavities can be detected. 2. In the chronic course of minor forms of thromboembolism of small branches of the pulmonary artery, local emphysema is formed. 3. At the early stages of COPD formation, regional zones of emphysematous restructuring of the lung tissue with a predominance of ventilation dysfunctions and zones of «compressive ischemia» with prevailing vascular disorders are formed. As the pathological process progresses, the ischemia factor acquires independent significance in the pathogenesis of the disease.

DuDoCFNet: Dual-Domain Coarse-to-Fine Progressive Network for Simultaneous Denoising, Limited-View Reconstruction, and Attenuation Correction of Cardiac SPECT.

Single-Photon Emission Computed Tomography (SPECT) is widely applied for the diagnosis of coronary artery diseases. Low-dose (LD) SPECT aims to minimize radiation exposure but leads to increased image noise. Limited-view (LV) SPECT, such as the latest GE MyoSPECT ES system, enables accelerated scanning and reduces hardware expenses but degrades reconstruction accuracy. Additionally, Computed Tomography (CT) is commonly used to derive attenuation maps (μ-maps) for attenuation correction (AC) of cardiac SPECT, but it will introduce additional radiation exposure and SPECT-CT misalignments. Although various methods have been developed to solely focus on LD denoising, LV reconstruction, or CT-free AC in SPECT, the solution for simultaneously addressing these tasks remains challenging and under-explored. Furthermore, it is essential to explore the potential of fusing cross-domain and cross-modality information across these interrelated tasks to further enhance the accuracy of each task. Thus, we propose a Dual-Domain Coarse-to-Fine Progressive Network (DuDoCFNet), a multi-task learning method for simultaneous LD denoising, LV reconstruction, and CT-free μ-map generation of cardiac SPECT. Paired dual-domain networks in DuDoCFNet are cascaded using a multi-layer fusion mechanism for cross-domain and cross-modality feature fusion. Two-stage progressive learning strategies are applied in both projection and image domains to achieve coarse-to-fine estimations of SPECT projections and CT-derived μ-maps. Our experiments demonstrate DuDoCFNet's superior accuracy in estimating projections, generating μ-maps, and AC reconstructions compared to existing single- or multi-task learning methods, under various iterations and LD levels. The source code of this work is available at https://github.com/XiongchaoChen/DuDoCFNet-MultiTask.

Abstract CT182: Oncolytic virus CF33-hNIS for the treatment of advanced cancer

Abstract Background: CF33-hNIS is a novel vaccinia virus engineered with the human sodium-iodide symporter (hNIS) gene. CF33-hNIS selectively replicates in tumor cells and promotes anti-tumor immunity. Here, we report results on a first-in-human phase 1 dose escalation study of CF33-hNIS, administered intratumorally (IT) or intravenously (IV) in adult patients with metastatic or advanced solid tumors (MAST). Methods: The MAST study is evaluating the safety of CF33-hNIS administered IT or IV, alone or in combination with pembrolizumab in patients with advanced or metastatic solid tumors with ≥ 2 prior lines of therapy (NCT05346484). CF33-hNIS is administered in 21-day cycles on C1D1 and C1D8, then D1 of each cycle thereafter. Pembrolizumab begins C2D1 for the combination groups and is administered Q3W. The study consists of two parts. Part 1 follows a 3+3 dose escalation scheme independent of each route of CF33-hNIS administration (IT and IV) and for each therapy regimen (monotherapy and combination therapy) with up to 7 dose levels of CF33-hNIS ranging from 8.6x105 to 3.0x109 PFU. Part 2 is a cohort expansion in select indications at the optimal dose. The co-primary endpoints are safety and identification of the recommended phase 2 dose. Secondary endpoints include objective response rate according to RECIST v1.1 and iRECIST, and assessment of viral replication in tumor lesions via Single-Photon Emission Computerized Tomography (SPECT). Results: As of Dec 2023, 36 patients have been treated in Part 1 of the study with a median age of 59 (range 23-81). Twenty-two (61%) patients were heavily pretreated with ≥3 prior lines of systemic therapy, and 14 (39%) received prior treatment with checkpoint blockade. Treatment-related adverse events consisted predominantly of ‘flu-like’ symptoms, such as grade 1/2: fatigue (31%), pyrexia (22%), and chills (14%). No dose-limiting toxicities have occurred. The highest dose treated to date is 1.1x108 PFU by IT and IV delivery; dose escalation continues. In the IT cohorts (14 patients), 7 of 15 (47%) injected lesions had a reduction in tumor burden, three lesions were completely eradicated. Three patients (21%) had an objective response: one complete response by iRECIST in a patient with cholangiocarcinoma; and two partial responses in patients with melanoma by RECIST. In IV cohorts (17 patients), 53% of patients achieved stable disease as their best response. Patients who received prior checkpoint blockade therapy derived clinical benefit with and without pembrolizumab. Viral replication, assessed by SPECT was higher in patients that saw a reduction in tumor burden. Immunological changes in peripheral blood and tumor biopsies will be presented. Conclusions: CF33-hNIS alone or in combination with pembrolizumab is a safe treatment option for advanced cancer patients. Encouraging efficacy has warranted advancement to part 2 of this study with a cohort expansion of patients with cholangiocarcinoma and other tumor types. Citation Format: Daneng Li, Anthony F. Shields, Hirva Mamdani, Patrick Travis, Gavin Wright, Wallace Akerley, Alex Spira, Gregory Daniels, Jaime Merchan, Abhijeet Kumar, Emerson Lim, Colt Egelston, Oscar Flores, Stanley Hamilton, Janet Austria, Amanda Seiz, Sharon Yavrom, Seymour Fein, John Byon, Paul Woodard, Grey A. Wilkinson, Jennifer Leddon. Oncolytic virus CF33-hNIS for the treatment of advanced cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT182.

Incorporation of Carboxylate Pendant Arms into 18-Membered Macrocycles: Effects on [nat/203Pb]Pb(II) Complexation.

We present a detailed investigation on the coordination chemistry of [nat/203Pb]Pb(II) with chelators H4PYTA and H4CHX-PYTA. These chelators belong to the family of ligands derived from the 18-membered macrocyclic backbone PYAN and present varying degrees of rigidity due to the presence of either ethyl or cyclohexyl spacers. A complete study of the stable Pb(II) complexes is carried out via NMR, X-Ray crystallography, stability constant determination and computational studies. While these studies indicated that Pb(II) complexation is achieved, and the thermodynamic stability of the resulting complexes is very high, a certain degree of fluxionality does exist in both cases. Nevertheless, radiolabeling studies were carried out using SPECT (single photon emission computed tomography) compatible isotope lead-203 (203Pb, t1/2=51.9 h), and while both chelators complex the radioisotope, the incorporation of carboxylate pendant arms appears to be detrimental towards the stability of the complexes when compared to the previously described amide analogues. Additionally, incorporation of a cyclohexyl spacer does not improve the kinetic inertness of the system.

NaI gamma camera performance for high energies: Effects of crystal thickness, photomultiplier tube geometry and light guide thickness.

Gamma camera imaging, including single photon emission computed tomography (SPECT), is crucial for research, diagnostics, and radionuclide therapy. Gamma cameras are predominantly based on arrays of photon multipliers tubes (PMTs) that read out NaI(Tl) scintillation crystals. In this way, standard gamma cameras can localize ɣ-rays with energies typically ranging from 30 to 360keV. In the last decade, there has been an increasing interest towards gamma imaging outside this conventional clinical energy range, for example, for theragnostic applications and preclinical multi-isotope positron emission tomography (PET) and PET-SPECT. However, standard gamma cameras are typically equipped with 9.5mm thick NaI(Tl) crystals which can result in limited sensitivity for these higher energies. Here we investigate to what extent thicker scintillators can improve the photopeak sensitivity for higher energy isotopes while attempting to maintain spatial resolution. Using Monte Carlo simulations, we analyzed multiple PMT-based configurations of gamma detectors with monolithic NaI (Tl) crystals of 20 and 40mm thickness. Optimized light guide thickness together with 2-inch round, 3-inch round, 60×60 mm2 square, and 76×76 mm2 square PMTs were tested. For each setup, we assessed photopeak sensitivity, energy resolution, spatial, and depth-of-interaction (DoI) resolution for conventional (140keV) and high (511keV) energy ɣ using a maximum-likelihood algorithm. These metrics were compared to those of a "standard" 9.5mm-thick crystal detector with 3-inch round PMTs. Estimated photopeak sensitivities for 511keV were 27% and 53% for 20 and 40mm thick scintillators, which is respectively, 2.2 and 4.4 times higher than for 9.5mm thickness. In most cases, energy resolution benefits from using square PMTs instead of round ones, regardless of their size. Lateral and DoI spatial resolution are best for smaller PMTs (2-inch round and 60×60 mm2 square) which outperform the more cost-effective larger PMT setups (3-inch round and 76×76 mm2 square), while PMT layout and shape have negligible (<10%) effect on resolution. Best spatial resolution was obtained with 60×60 mm2 PMTs; for 140keV, lateral resolution was 3.5mm irrespective of scintillator thickness, improving to 2.8 and 2.9mm for 511keV with 20 and 40mm thick crystals, respectively. Using the 3-inch round PMTs, lateral resolutions of 4.5 and 3.9mm for 140keV and of 3.5 and 3.7mm for 511keV were obtained with 20 and 40mm thick crystals respectively, indicating a moderate performance degradation compared to the 3.5 and 2.9mm resolution obtained by the standard detector for 140 and 511keV. Additionally, DoI resolution for 511keV was 7.0 and 5.6mm with 20 and 40mm crystals using 60×60 mm2 square PMTs, while with 3-inch round PMTs 12.1 and 5.9mm were obtained. Depending on PMT size and shape, the use of thicker scintillator crystals can substantially improve detector sensitivity at high gamma energies, while spatial resolution is slightly improved or mildly degraded compared to standard crystals.

[Update on endocarditis 2024].

Infective endocarditis (IE) is alife-threatening disease with an increasing incidence despite improved preventive measures. The revision of the European Society of Cardiology (ESC) guidelines on infective endocarditis in 2023 brings significant innovations in prevention, diagnostics, and treatment. Many measures for prophylaxis and prevention have been more clearly defined and given higher recommendation levels. In the diagnostics of IE the use of other imaging modalities besides echocardiography, such as cardiac computed tomography (CT), positron emission tomography (PET)/CT or single photon emission computed tomography (SPECT)/CT with radioactively labeled leukocytes was more strongly emphasized. The diagnostics and treatment of IE associated with a cardiac implantable electronic device (CIED) were also revised. An essential innovation is also the possibility of an outpatient antibiotic treatment for certain patients after initial treatment in hospital. The indications for surgery have also been revised and, in particular, the timing of surgery has been more clearly defined. This article provides an overview of the most important changes.

Synthesis of Novel Plant-Derived Encapsulated Radiolabeled Compounds for the Diagnosis of Parkinson's Disease and the Evaluation of Biological Effects with In Vitro/In Vivo Methods.

Parkinson's disease (PD) is a neurodegenerative disorder that affects millions of individuals globally. It is characterized by the loss of dopaminergic neurons in Substantia Nigra pars compacta (SNc) and striatum. Neuroimaging techniques such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI) help diagnosing PD. In this study, the focus was on developing technetium-99m ([99mTc]Tc) radiolabeled drug delivery systems using plant-derived compounds for the diagnosis of PD. Madecassoside (MA), a plant-derived compound, was conjugated with Levodopa (L-DOPA) to form MA-L-DOPA, which was then encapsulated using Poly Lactic-co-Glycolic Acid (PLGA) to create MA-PLGA and MA-L-DOPA-PLGA nanocapsules. Extensive structural analysis was performed using various methods such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), liquid chromatography-mass spectrometry (LC-MS), thin layer chromatography (TLC), high performance liquid chromatography (HPLC), dynamic light scattering (DLS), and scanning electron microscopy (SEM) to characterize the synthesized products. Radiochemical yields of radiolabeled compounds were determined using thin layer radio chromatography (TLRC) and high performance liquid radio chromatography (HPLRC) methods. In vitro cell culture studies were conducted on human neuroblastoma (SH-SY5Y) and rat pheochromocytoma (PC-12) cell lines to assess the incorporation of [99mTc]Tc radiolabeled compounds ([99mTc]Tc-MA, [99mTc]Tc-MA-L-DOPA, [99mTc]Tc-MA-PLGA and [99mTc]Tc-MA-L-DOPA-PLGA) and the cytotoxicity of inactive compounds (MA and MA-L-DOPA compounds and encapsulated compounds (MA-PLGA and MA-L-DOPA-PLGA). Additionally, the biodistribution studies were carried out on healthy male Sprague-Dawley rats and a Parkinson's disease experimental model to evaluate the compounds' bioactivity using the radiolabeled compounds. The radiochemical yields of all radiolabeled compounds except [99mTc]Tc-L-DOPA-PLGA were above 95% and had stability over 6h. The cytotoxic effects of all substances on SH-SY5Y and PC-12 cells increase with increasing concentration values. The uptake values of PLGA-encapsulated compounds are statistically significant in SH-SY5Y and PC-12 cells. The biodistribution studies showed that [99mTc]Tc-MA is predominantly retained in specific organs and brain regions, with notable uptake in the prostate, muscle, and midbrain. PLGA-encapsulation led to higher uptake in certain organs, suggesting its biodegradable nature may enhance tissue retention, and surface modifications might further optimize brain penetration. Overall, the results indicate that radiolabeled plant-derived encapsulated drug delivery systems with [99mTc]Tc hold potential as diagnostic agents for PD symptoms. This study contributes to the advancement of drug delivery agents in the field of brain research.

Advancing multimodal medical image fusion: an adaptive image decomposition approach based on multilevel Guided filtering.

With the rapid development of medical imaging methods, multimodal medical image fusion techniques have caught the interest of researchers. The aim is to preserve information from diverse sensors using various models to generate a single informative image. The main challenge is to derive a trade-off between the spatial and spectral qualities of the resulting fused image and the computing efficiency. This article proposes a fast and reliable method for medical image fusion depending on multilevel Guided edge-preserving filtering (MLGEPF) decomposition rule. First, each multimodal medical image was divided into three sublayer categories using an MLGEPF decomposition scheme: small-scale component, large-scale component and background component. Secondly, two fusion strategies-pulse-coupled neural network based on the structure tensor and maximum based-are applied to combine the three types of layers, based on the layers' various properties. The three different types of fused sublayers are combined to create the fused image at the end. A total of 40 pairs of brain images from four separate categories of medical conditions were tested in experiments. The pair of images includes various case studies including magnetic resonance imaging (MRI) , TITc, single-photon emission computed tomography (SPECT) and positron emission tomography (PET). We included qualitative analysis to demonstrate that the visual contrast between the structure and the surrounding tissue is increased in our proposed method. To further enhance the visual comparison, we asked a group of observers to compare our method's outputs with other methods and score them. Overall, our proposed fusion scheme increased the visual contrast and received positive subjective review. Moreover, objective assessment indicators for each category of medical conditions are also included. Our method achieves a high evaluation outcome on feature mutual information (FMI), the sum of correlation of differences (SCD), Qabf and Qy indexes. This implies that our fusion algorithm has better performance in information preservation and efficient structural and visual transferring.

PET and SPECT imaging as a solid guide to detect and discriminate atypical phenotypes of neurodegenerative disorders

Introduction and aim. Atypical or mixed presentations of neurodegenerative disorders may postpone or confound the final diagnosis. Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) radioligands provide target-specific information and may anticipate the diagnosis by “in vivo” detection of the neuro pathological substrate, as Aβ deposition, nigrostriatal dopaminergic depletion or tau inclusions. This concise review will dis cuss the potential of PET and SPECT imaging as a solid guide to better characterize atypical phenotypes of neurodegeneration in the clinical routine, with the potential to drive personalized interventions, improve cohort uniformity for clinical trials, and serve as biomarkers for targeted molecular therapies. Material and methods. Literature search was performed focusing on the role of PET and SPECT imaging in assessing atypical phenotypes of neurodegeneration, using the electronic source of database PubMed/MEDLINE and the web-based search engines Google, Google Scholar. Analysis of the literature. New disease-modifying drugs may increase their effect with early initiation, which is especially im portant in working persons and younger subjects presenting atypical symptoms. In older individuals, the coexistence of neu rodegeneration, age-related changes, cerebrovascular lesions, or depression makes challenging a definitive diagnosis. Quantitative tools able to measure tracer distribution increase the accuracy of molecular neuroimaging creating topographic maps that compare subject’s data with healthy controls databases. Conclusion. Atypical phenotypes may be associated with quantitative key-pattern allowing a more precise and early diagnosis of the neurodegenerative disorder. Finally, quantitative assessment of the pathological substrates allows us to track the disease process and measure treatment response.