SPECT/CT of Total Ankle Arthroplasty.

Use of SPECT/CT (Single Photon Emission Computed Tomography/Computed Tomography) is increasing providing additional information in patients with inconclusive clinical examination and unremarkable imaging findings presenting with chronic pain after total ankle arthroplasty. To differentiate the cause of pain after total ankle arthroplasty can be challenging. SPECT/CT combines structural and metabolic imaging as a hybrid tool leading to higher specificity and overall diagnostic accuracy presumably in cases of gutter impingement, prosthetic loosening, and osteoarthritis of adjacent joints. Moreover, SPECT/CT can complement diagnostic work up in periprosthetic joint infections. Basal tracer enhancement has to be considered for the interpretation of imaging findings.

Nuclear Imaging in Orthopaedic Practice: A Critical Analysis Review.

¼ Nuclear imaging techniques, including bone scintigraphy, labeled leukocyte scintigraphy, positron emission tomography (PET), and single-photon emission computed tomography (SPECT) combined with computed tomography (CT), have wide applications in orthopaedics for evaluating trauma, painful total joint arthroplasty, musculoskeletal infection, and orthopaedic oncology.¼ Three-phase bone scintigraphy is a first-line, highly sensitive nuclear medicine study for evaluating orthopaedic pathology when initial studies are inconclusive. However, its specificity is limited, and findings may be falsely positive for up to 2 years after total joint arthroplasty because of physiologic bone remodeling.¼ Labeled leukocyte scintigraphy or gallium scintigraphy can improve diagnostic accuracy in patients with a positive bone scan and suspected musculoskeletal or periprosthetic joint infection.¼ 18-Fluorodeoxyglucose PET/CT demonstrates high sensitivity and specificity for diagnosing bone neoplasms, infections, and metabolic disorders. Emerging PET/magnetic resonance imaging technology offers reduced radiation exposure and greater soft-tissue detail but presents technical and cost challenges.¼ SPECT/CT provides valuable functional and anatomic detail for characterizing the extent and location of bone pathology, serving as an important adjunct to other imaging modalities.¼ Ultimately, the choice of nuclear imaging modality should consider the specific clinical context, diagnostic accuracy, impact on management, and cost-effectiveness on a case-by-case basis.

Radiotracers for Molecular Imaging of Angiotensin-Converting Enzyme 2.

Angiotensin-converting enzymes (ACE) are well-known for their roles in both blood pressure regulation via the renin-angiotensin system as well as functions in fertility, immunity, hematopoiesis, and many others. The two main isoforms of ACE include ACE and ACE-2 (ACE2). Both isoforms have similar structures and mediate numerous effects on the cardiovascular system. Most remarkably, ACE2 serves as an entry receptor for SARS-CoV-2. Understanding the interaction between the virus and ACE2 is vital to combating the disease and preventing a similar pandemic in the future. Noninvasive imaging techniques such as positron emission tomography and single photon emission computed tomography could noninvasively and quantitatively assess in vivo ACE2 expression levels. ACE2-targeted imaging can be used as a valuable tool to better understand the mechanism of the infection process and the potential roles of ACE2 in homeostasis and related diseases. Together, this information can aid in the identification of potential therapeutic drugs for infectious diseases, cancer, and many ACE2-related diseases. The present review summarized the state-of-the-art radiotracers for ACE2 imaging, including their chemical design, pharmacological properties, radiochemistry, as well as preclinical and human molecular imaging findings. We also discussed the advantages and limitations of the currently developed ACE2-specific radiotracers.

Intestinal fatty acid binding protein is associated with infarct size and cardiac function in acute heart failure following myocardial infarction.

BACKGROUND: In acute heart failure (HF), reduced cardiac output, vasoconstriction and congestion may damage the intestinal mucosa and disrupt its barrier function. This could facilitate the leakage of bacterial products into circulation and contribute to inflammation and adverse cardiac remodelling. We aimed to investigate gut leakage markers and their associations with inflammation, infarct size and cardiac function. METHODS: We examined 61 ST-elevation myocardial infarction (STEMI) patients who developed acute HF within 48 hours of successful percutaneous coronary intervention (PCI). Serial blood samples were taken to measure lipopolysaccharide (LPS), LPS-binding protein (LBP), soluble cluster of differentiation 14 (sCD14) and intestinal fatty acid binding protein (I-FABP). Cumulative areas under the curve (AUCs) from baseline to day 5 were calculated. Serial echocardiography was performed to assess left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and wall motion score index (WMSI). Single-photon emission CT (SPECT) was performed at 6 weeks to determine infarct size and LVEF. RESULTS: I-FABPAUC correlated positively with infarct size (rs=0.45, p=0.002), GLS (rs=0.32, p=0.035) and WMSI (rs=0.45, p=0.002) and negatively with LVEF measured by SPECT (rs=-0.40, p=0.007) and echocardiography (rs=-0.33, p=0.021) at 6 weeks. LPSAUC, LBPAUC and sCD14AUC did not correlate to any cardiac function marker or infarct size. Patients, who at 6 weeks had above median GLS and WMSI, and below-median LVEF measured by SPECT, were more likely to have above median I-FABPAUC during admission (adjusted OR (aOR) 5.22, 95% CI 1.21 to 22.44; aOR 5.05, 95% CI 1.25 to 20.43; aOR 5.67, 95% CI 1.42 to 22.59, respectively). The same was observed for patients in the lowest quartile of LVEF measured by echocardiography (aOR 9.99, 95% CI 1.79 to 55.83) and three upper quartiles of infarct size (aOR 20.34, 95% CI 1.56 to 264.65). CONCLUSIONS: In primary PCI-treated STEMI patients with acute HF, I-FABP, a marker of intestinal epithelial damage, was associated with larger infarct size and worse cardiac function after 6 weeks.

Acetyl-DL-leucine in two individuals with REM sleep behavior disorder improves symptoms, reverses loss of striatal dopamine-transporter binding and stabilizes pathological metabolic brain pattern-case reports.

Isolated REM Sleep Behavior Disorder (iRBD) is considered a prodrome of Parkinson's disease (PD). We investigate whether the potentially disease-modifying compound acetyl-DL-leucine (ADLL; 5 g/d) has an effect on prodromal PD progression in 2 iRBD-patients. Outcome parameters are RBD-severity sum-score (RBD-SS-3), dopamine-transporter single-photon emission computerized tomography (DAT-SPECT) and metabolic "Parkinson-Disease-related-Pattern (PDRP)"-z-score in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). After 3 weeks ADLL-treatment, the RBD-SS-3 drops markedly in both patients and remains reduced for >18 months of ADLL-treatment. In patient 1 (female), the DAT-SPECT putaminal binding ratio (PBR) decreases in the 5 years pretreatment from normal (1.88) to pathological (1.22) and the patient's FDG-PET-PDRP-z-score rises from 1.72 to 3.28 (pathological). After 22 months of ADLL-treatment, the DAT-SPECT-PBR increases to 1.67 and the FDG-PET-PDRP-z-score stabilizes at 3.18. Similar results are seen in patient 2 (male): his DAT-SPECT-PBR rises from a pretreatment value of 1.42 to 1.72 (close to normal) and the FDG-PET-PDRP-z-score decreases from 1.02 to 0.30 after 18 months of ADLL-treatment. These results support exploration of whether ADLL may have disease-modifying properties in prodromal PD.

Relationship Between Infarct Artery, Myocardial Injury, and Outcomes After Primary Percutaneous Coronary Intervention in ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: The extent to which infarct artery impacts the extent of myocardial injury and outcomes in patients with ST-segment-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention is uncertain. METHODS AND RESULTS: We performed a pooled analysis using individual patient data from 7 randomized STEMI trials in which myocardial injury within 30 days after primary percutaneous coronary intervention was assessed in 1774 patients by cardiac magnetic resonance (n=1318) or technetium-99m sestamibi single-photon emission computed tomography (n=456). Clinical follow-up was performed at a median duration of 351 days (interquartile range, 184-368 days). Infarct size and outcomes were assessed in anterior (infarct vessel=left anterior descending) versus nonanterior (non-left anterior descending) STEMI. Median infarct size (percentage left ventricular myocardial mass) was larger in patients with anterior compared with nonanterior STEMI (19.7% [interquartile range, 9.4%-31.7%] versus 12.6% [interquartile range, 5.1%-20.5%]; P<0.001). Patients with anterior compared with nonanterior STEMI were at higher risk for 1-year all-cause mortality (6.2% versus 3.6%; adjusted hazard ratio [HR], 1.66 [95% CI, 1.02-2.69]; P=0.04) and heart failure hospitalization (4.4% versus 2.6%; adjusted HR, 1.96 [95% CI, 1.15-3.36]; P=0.01). Infarct size was a predictor of subsequent all-cause mortality or heart failure hospitalization in anterior STEMI (adjusted HR per 1% increase, 1.05 [95% CI, 1.03-1.07]; P<0.001), but not in nonanterior STEMI (adjusted HR, 1.02 [95% CI, 0.99-1.05]; P=0.19). The P value for this interaction was 0.04. CONCLUSIONS: Anterior STEMI was associated with substantially greater myonecrosis after primary percutaneous coronary intervention compared with nonanterior STEMI, contributing in large part to the worse prognosis in patients with anterior infarction.

Path Integration Detects Prodromal Alzheimer's Disease and Predicts Cognitive Decline.

Background: The entorhinal cortex is the very earliest involvement of Alzheimer's disease (AD). Grid cells in the medial entorhinal cortex form part of the spatial navigation system. Objective: We aimed to determine whether path integration performance can be used to detect patients with mild cognitive impairment (MCI) at high risk of developing AD, and whether it can predict cognitive decline. Methods: Path integration performance was assessed in 71 patients with early MCI (EMCI) and late MCI (LMCI) using a recently developed 3D virtual reality navigation task. Patients with LMCI were further divided into those displaying characteristic brain imaging features of AD, including medial temporal lobe atrophy on magnetic resonance imaging and posterior hypoperfusion on single-photon emission tomography (LMCI+), and those not displaying such features (LMCI-). Results: Path integration performance was significantly lower in patients with LMCI+than in those with EMCI and LMCI-. A significantly lower performance was observed in patients who showed progression of MCI during 12 months, than in those with stable MCI. Path integration performance distinguished patients with progressive MCI from those with stable MCI, with a high classification accuracy (a sensitivity of 0.88 and a specificity of 0.70). Conclusions: Our results suggest that the 3D virtual reality navigation task detects prodromal AD patients and predicts cognitive decline after 12 months. Our navigation task, which is simple, short (12-15 minutes), noninvasive, and inexpensive, may be a screening tool for therapeutic choice of disease-modifiers in individuals with prodromal AD.

Utility of neuromelanin-sensitive MRI in the diagnosis of dementia with Lewy bodies.

OBJECTIVE: Dementia with Lewy bodies (DLB) is recognized as the second most common cause of degenerative dementia in older people with Alzheimer's disease (AD), and distinguishing between these 2 diseases may be challenging in clinical practice. However, accurate differentiation is important because these 2 diseases have different prognoses and require different care. Recently, several studies have reported that neuromelanin-sensitive MRI can detect neurodegeneration in the substantia nigra pars compacta (SNc). DLB patients are considered to demonstrate degeneration and a reduction of dopaminergic neurons in the SNc. Therefore, neuromelanin-sensitive MRI may be useful for the diagnosis of DLB. Therefore, in this study, we aimed to investigate the usefulness of neuromelanin-sensitive MRI in the distinguishing DLB from AD. METHODS: A total of 21 probable DLB and 22 probable AD patients were enrolled. All participants underwent both DaT-SPECT and neuromelanin-sensitive MRI. A combined model of neuromelanin-sensitive MRI and Dopamine transporter single-photon emission computed tomography (DaT-SPECT) was created using logistic regression analysis (forced entry method). RESULTS: There was no difference in the diagnostic utility of neuromelanin-sensitive MRI and DaT-SPECT in distinguishing DLB from AD. There was no significant correlation between the results of neuromelanin-sensitive MRI and DaT-SPECT in DLB patients. The combination of neuromelanin-sensitive MRI and DaT-SPECT demonstrated higher diagnostic performance in distinguishing between DLB and AD compared with neuromelanin-sensitive MRI alone. Additionally, although the combination of both modalities showed a larger AUC compared with DaT-SPECT alone, the difference was not statistically significant. CONCLUSIONS: Neuromelanin-sensitive MRI may be equally or even more useful than DaT-SPECT in the clinical differentiation of DLB from AD. Furthermore, the combination of neuromelanin-sensitive MRI and DaT-SPECT may be a highly sensitive imaging marker for distinguishing DLB from AD.

Clinical performance of deep learning-enhanced ultrafast whole-body scintigraphy in patients with suspected malignancy.

BACKGROUND: To evaluate the clinical performance of two deep learning methods, one utilizing real clinical pairs and the other utilizing simulated datasets, in enhancing image quality for two-dimensional (2D) fast whole-body scintigraphy (WBS). METHODS: A total of 83 patients with suspected bone metastasis were retrospectively enrolled. All patients underwent single-photon emission computed tomography (SPECT) WBS at speeds of 20 cm/min (1x), 40 cm/min (2x), and 60 cm/min (3x). Two deep learning models were developed to generate high-quality images from real and simulated fast scans, designated 2x-real and 3x-real (images from real fast data) and 2x-simu and 3x-simu (images from simulated fast data), respectively. A 5-point Likert scale was used to evaluate the image quality of each acquisition. Accuracy, sensitivity, specificity, and the area under the curve (AUC) were used to evaluate diagnostic efficacy. Learned perceptual image patch similarity (LPIPS) and the Fréchet inception distance (FID) were used to assess image quality. Additionally, the count-level consistency of WBS was compared between the two models. RESULTS: Subjective assessments revealed that the 1x images had the highest general image quality (Likert score: 4.40 ± 0.45). The 2x-real, 2x-simu and 3x-real, 3x-simu images demonstrated significantly better quality than the 2x and 3x images (Likert scores: 3.46 ± 0.47, 3.79 ± 0.55 vs. 2.92 ± 0.41, P < 0.0001; 2.69 ± 0.40, 2.61 ± 0.41 vs. 1.36 ± 0.51, P < 0.0001), respectively. Notably, the quality of the 2x-real images was inferior to that of the 2x-simu images (Likert scores: 3.46 ± 0.47 vs. 3.79 ± 0.55, P = 0.001). The diagnostic efficacy for the 2x-real and 2x-simu images was indistinguishable from that of the 1x images (accuracy: 81.2%, 80.7% vs. 84.3%; sensitivity: 77.27%, 77.27% vs. 87.18%; specificity: 87.18%, 84.63% vs. 87.18%. All P > 0.05), whereas the diagnostic efficacy for the 3x-real and 3x-simu was better than that for the 3x images (accuracy: 65.1%, 66.35% vs. 59.0%; sensitivity: 63.64%, 63.64% vs. 64.71%; specificity: 66.67%, 69.23% vs. 55.1%. All P < 0.05). Objectively, both the real and simulated models achieved significantly enhanced image quality from the accelerated scans in the 2x and 3x groups (FID: 0.15 ± 0.18, 0.18 ± 0.18 vs. 0.47 ± 0.34; 0.19 ± 0.23, 0.20 ± 0.22 vs. 0.98 ± 0.59. LPIPS: 0.17 ± 0.05, 0.16 ± 0.04 vs. 0.19 ± 0.05; 0.18 ± 0.05, 0.19 ± 0.05 vs. 0.23 ± 0.04. All P < 0.05). The count-level consistency with the 1x images was excellent for all four sets of model-generated images (P < 0.0001). CONCLUSIONS: Ultrafast 2x speed (real and simulated) images achieved comparable diagnostic value to that of standardly acquired images, but the simulation algorithm does not necessarily reflect real data.

Radiolabeled Probes from Derivatives of Natural Compounds Used in Nuclear Medicine.

Natural compounds are important precursors for the synthesis of new drugs. The development of novel molecules that are useful for various diseases is the main goal of researchers, especially for the diagnosis and treatment of many diseases. Some pathologies need to be treated with radiopharmaceuticals, and, for this reason, radiopharmaceuticals that use the radiolabeling of natural derivates molecules are arousing more and more interest. Radiopharmaceuticals can be used for both diagnostic and therapeutic purposes depending on the radionuclide. ß+- and gamma-emitting radionuclides are used for diagnostic use for PET or SPECT imaging techniques, while α- and ß--emitting radionuclides are used for in metabolic radiotherapy. Based on these assumptions, the purpose of this review is to highlight the studies carried out in the last ten years, to search for potentially useful radiopharmaceuticals for nuclear medicine that use molecules of natural origin as lead structures. In this context, the main radiolabeled compounds containing natural products as scaffolds are analyzed, in particular curcumin, stilbene, chalcone, and benzofuran. Studies on structural and chemical modifications are emphasized in order to obtain a collection of potential radiopharmaceuticals that exploit the biological properties of molecules of natural origin. The radionuclides used to label these compounds are 68Ga, 44Sc, 18F, 64Cu, 99mTc, and 125I for diagnostic imaging.

Blunted tachycardia and cardiac sympathetic denervation in isolated rapid eye movement sleep behavior disorder.

BACKGROUND: Isolated rapid eye movement sleep behavior disorder (iRBD) serves as a prodromal phase of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Blunted tachycardia (BT) during postural changes indicates neurogenic orthostatic hypotension, a marker of autonomic dysfunction. We aimed to investigate whether BT is associated with cardiac sympathetic neurogenic denervation. Additionally, we conducted a preliminary short-term follow-up to examine the potential prognostic significance of BT regarding phenoconversion and mortality. METHODS: Forty-three patients with iRBD at Shiga University of Medical Science Hospital underwent active standing tests to identify BT, defined by a specific ratio of decrease in systolic blood pressure to inadequate increase in heart rate after standing, and orthostatic hypotension. 123I-metaiodobenzylguanidine myocardial scintigraphy (123I-MIBG) and dopamine transporter single-photon emission computed tomography (DAT-SPECT) were performed. Participants were followed up for 3.4 ± 2.4 years for phenoconversion and 4.0 ± 2.3 years for mortality assessment, and the risk of events was analyzed using log-rank tests. RESULTS: Among the 43 participants (mean age, 72.3 ± 7.9 years; 8 female), 17 met the BT criteria. We found no significant comorbidity-related differences in hypertension or diabetes between the BT(+) and BT(-) groups. Orthostatic hypotension was more prevalent in the BT(+) group than in the BT(-) group (47.1% vs 7.7%, p = 0.003). BT(+) patients were older with a lower early and delayed MIBG uptake; however, no significant differences were observed in DAT accumulation. Phenoconversion was observed in seven (41.2%) BT(+) and seven (26.9%) BT(-) patients. Three deaths were recorded in the BT(+) group (17.6%) and three in the BT(-) group (11.5%). No significant differences were observed in the risk of phenoconversion or mortality between the groups. CONCLUSIONS: We have identified the possibility that BT reflects cardiac sympathetic neurogenic denervation in patients with iRBD. Future research is needed to elucidate the potential prognostic value of BT.

Involvement of the nigrostriatal system in Gerstman-Sträussler-Scheinker disease with the PRNP-P102L mutation.

INTRODUCTION: Gerstmann-Sträussler-Scheinker disease (GSS) is an autosomal-dominant inherited prion disease most often associated with the human prion protein gene (PRNP)-P102L mutation. Although patients manifest considerable phenotypic heterogeneity, the involvement of the nigrostriatal system has not been well-studied. METHODS: We performed dopamine transporter single-photon emission computed tomography (DAT-SPECT) using 123I-ioflupane to investigate the nigrostriatal system function in nine patients with the PRNP-P102L mutation. We also examined the pathological findings in another patient whose predominant feature was ataxia and who died 5 years after disease onset. RESULTS: Striatum uptake of 123I-ioflupane indicated by specific binding ratio (SBR) values was significantly reduced in two patients. The DAT-SPECT examination was performed 6 months after disease onset in one of these patients who manifested rapidly developing cognitive decline mimicking Creutzfeldt-Jakob disease. DAT-SPECT was also performed 9 years after disease onset in another patient who manifested the conventional features of GSS involving ataxia and dementia in the initial phase but showed akinetic mutism at the examination time. Another patient examined 2 years after disease onset who predominantly manifested ataxia showed marginally abnormal SBR values. An autopsy case showed moderate neuronal loss in the substantia nigra, and the degree of neuronal loss was similar in most other parts of the brain. CONCLUSION: Nigrostriatal system involvement may occur in patients with GSS associated with the PRNP-P102L mutation, even though parkinsonism is not the predominant feature.

Enhanced Diagnostic Accuracy of Pulmonary Embolism: Integrating Low-Dose CT with V/Q SPECT.

OBJECTIVE: This study aimed to retrospectively assess the benefits of combining low-dose computed tomography (LDCT) with ventilation/perfusion single-photon emission computed tomography (V/Q SPECT) for the diagnosis of pulmonary embolism (PE). METHODS: A retrospective analysis was performed on 92 patients with suspected PE who underwent V/Q SPECT with ldCT (V/Q SPECT CT) between January 2020 and December 2022 at King Khalid Hospital Najran. Data were collected using the hospital's picture archiving and communication system. Scans were categorized on the basis of perfusion defects, matched or mismatched ventilation, and CT findings. The specificity of V/Q SPECT CT was compared with that of Q SPECT CT. RESULTS: This study included 92 patients (54 females and 38 males; median age, 53 years). The results demonstrated that V/Q SPECT CT had higher specificity (93%) than V/Q SPECT alone (88%). If CT had been used as a ventilation substitute, 21% of patients would have been reported to be positive for PE (8% false-positive), yielding a specificity of 60% for Q SPECT CT. These findings align with the existing literature, although discrepancies in specificity values were noted due to the different study designs and sample sizes. CONCLUSION: This study highlights the enhanced specificity of V/Q SPECT CT compared to V/Q SPECT and Q SPECT CT alone. Including low-dose CT improves diagnostic accuracy by reducing false positives and providing detailed anatomical information. V/Q SPECT CT offers superior specificity in diagnosing PE compared with V/Q SPECT alone, supporting its use in clinical practice.

Impairment of hippocampal astrocyte-mediated striatal dopamine release and locomotion in Alzheimer's disease.

BACKGROUND: Clinical and translational research has identified deficits in the dopaminergic neurotransmission in the striatum in Alzheimer's disease (AD) and this could be related to the pathophysiology of psychiatric symptoms appearing even at early stages of the pathology. HYPOTHESIS: We hypothesized that AD pathology in the hippocampus may influence dopaminergic neurotransmission even in the absence of AD-related lesion in the mesostriatal circuit. METHODS: We chemogenetically manipulated the activity of hippocampal neurons and astrocytes in wild-type and hemizygous TgF344-AD (Tg) rats, an animal model of AD pathology. We assessed the brain-wide functional output of this manipulation using in vivo Single Photon Emission Computed Tomography to measure cerebral blood flow and D2/3 receptor binding, in response to acute (3 mg kg-1 i.p.) and chronic (0.015 mg/ml in drinking water, 28 days) stimulation of neurons or astrocytes with clozapine N-oxide. We also assessed the effects of the chronic chemogenetic manipulations on D2 receptor density, low or high aggregated forms of amyloid Aß40 and Aß42, astrocytes and microglial reactivity, and the capacity of astrocytes and microglia to surround and phagocytize Aß both locally and in the striatum. RESULTS: We showed that acute and chronic neuronal and astrocytic stimulation induces widespread effects on the brain regional activation pattern, notably with an inhibition of striatal activation. In the Tg rats, both these effects were blunted. Chemogenetic stimulation in the hippocampus increased microglial density and its capacity to limit AD pathology, whereas these effects were absent in the striatum perhaps as a consequence of the altered connectivity between the hippocampus and the striatum. CONCLUSIONS: Our work suggests that hippocampal AD pathology may alter mesostriatal signalling and induce widespread alterations of brain activity. Neuronal and astrocytic activation may induce a protective, Aß-limiting phenotype of microglia, which surrounds Aß plaques and limits Αß concentration more efficiently.

99mTc-HYNIC-Annexin V detection of apoptosis in the rabbit model of liver cancer.

To investigate the feasibility of detection of apoptosis in vivo by 99mTc-HYNIC-Annexin V, Annexin V was labeled with 99mTc through HYNIC. 18 New Zealand rabbits implanted VX-2 were randomly divided into control (n = 8) and paclitaxel (PAC, n = 10) groups, given 2 mL/kg of normal saline or 2.4 mg/kg of PAC intravenously. The liver tumor imaging was detected by SPECT through intravenous injection of 99mTc-HYNIC-Annexin V before treatment, 24 hours and 48 hours after treatment respectively. Tumor radioactive count proportion to non-tumor sites was calculated. When the last imaging was finished, the rabbits were sacrificed. The tumor was taken out and divided into two pieces, one for TUNEL immunohistochemical analysis and the other for flow cytometry (FCM). We found that the rate of Annexin V labeled with 99mTc through HYNIC was more than 95%, and radiochemical purity was above 95%. The SPECT showed that two groups had no significant tumor imaging before the treatment. There is no significant tumor imaging in control group, while the PAC group 24 h and 48 h after treatment showed significant accumulation. The Tumor/non-Tumor (T/NT) in PAC group at 24 h and 48 h after chemotherapy was significantly different from that in the control group and PAC group prior to treatment. There was no significant difference between 24 h and 48 h in PAC group. The TUNEL-positive cells detected by immunohistochemistry and apoptotic rate detected by FCM in PAC group were significant different from those in control group. The T/NT was significantly correlated to TUNEL-positive cells and apoptotic rate of the tumor. PAC can induce apoptosis of rabbit VX-2 liver cancer cells. 24-48 h after paclitaxel chemotherapy is a window time for apoptosis detection. Apoptotic cells in vivo can be detected by SPECT through 99mTc-HYNIC-Annexin V.

[Improvement of the technique of positioning the endocardial electrodes of the cardiac contractility modulation device in patients with CHF with reduced ejection fraction and atrial fibrillation].

AIM: To evaluate the efficacy and safety of the advanced technique for positioning the endocardial electrodes of a cardiac contractility modulation (CCM) device. MATERIALS AND METHODS: The CCM system was implanted in 100 patients, of which 60 CCM electrodes were positioned in the most optimal zones of myocardial perfusion, in particular, in the zone of the minor focal-scar/fibrotic lesion (the Summed Rest Score of 0 to 1-2, the intensity of the radiopharmaceutical at least 30%), and in 40 patients according to the standard procedure. Before the implantation of the CCM system, 60 patients underwent tomography (S-SPECT) of the myocardium with 99mTc-methoxy-isobutyl-isonitrile at rest to determine the most optimal electrode positioning zones and 100 patients underwent transthoracic echocardiography at baseline and after 12 months to assess the effectiveness of surgical treatment. RESULTS: Improved ventricular electrode positioning technique is associated with the best reverse remodeling of the left ventricular myocardium, especially in patients with ischemic chronic heart failure, with less radiation exposure to the surgeon and the patient, and without electrode-related complications. CONCLUSION: At the preoperative stage, it is recommended to perform a synchronized single-photon emission computed tomography of the myocardium with 99mTc-methoxy-isobutyl-isonitrile at rest before implantation of the CCM device to assess the presence of scar zones/myocardial fibrosis in the anterior and inferior septal regions of the interventricular septum of the left ventricle, followed by implantation of ventricular electrodes in the zone of the minor scar/fibrous lesion, which will allow to achieve optimal stimulation parameters, increase the effectiveness of CCM therapy, reduce the radiation exposure on medical personnel and the patient during surgery.

Unrealistic Data Augmentation Improves the Robustness of Deep Learning-Based Classification of Dopamine Transporter SPECT Against Variability Between Sites and Between Cameras.

We propose strongly unrealistic data augmentation to improve the robustness of convolutional neural networks (CNNs) for automatic classification of dopamine transporter SPECT against the variability between sites and between cameras. Methods: A CNN was trained on a homogeneous dataset comprising 1,100 123I-labeled 2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)nortropane SPECT images using strongly unrealistic data augmentation based on gaussian blurring and additive noise. Strongly unrealistic data augmentation was compared with no augmentation and intensity-based nnU-Net augmentation on 2 independent datasets with lower (n = 645) and considerably higher (n = 640) spatial resolution. Results: The CNN trained with strongly unrealistic augmentation achieved an overall accuracy of 0.989 (95% CI, 0.978-0.996) and 0.975 (95% CI, 0.960-0.986) in the independent test datasets, which was better than that without (0.960, 95% CI, 0.942-0.974; 0.953, 95% CI, 0.934-0.968) and with nnU-Net augmentation (0.972, 95% CI, 0.956-0.983; 0.950, 95% CI, 0.930-0.966) (all McNemar P < 0.001). Conclusion: Strongly unrealistic data augmentation results in better generalization of CNN-based classification of 123I-labeled 2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)nortropane SPECT images to unseen acquisition settings. We hypothesize that this can be transferred to other nuclear imaging applications.

Image-guided patient-specific optimization of catheter placement for convection-enhanced nanoparticle delivery in recurrent glioblastoma.

BACKGROUND: Proper catheter placement for convection-enhanced delivery (CED) is required to maximize tumor coverage and minimize exposure to healthy tissue. We developed an image-based model to patient-specifically optimize the catheter placement for rhenium-186 (186Re)-nanoliposomes (RNL) delivery to treat recurrent glioblastoma (rGBM). METHODS: The model consists of the 1) fluid fields generated via catheter infusion, 2) dynamic transport of RNL, and 3) transforming RNL concentration to the SPECT signal. Patient-specific tissue geometries were assigned from pre-delivery MRIs. Model parameters were personalized with either 1) individual-based calibration with longitudinal SPECT images, or 2) population-based assignment via leave-one-out cross-validation. The concordance correlation coefficient (CCC) was used to quantify the agreement between the predicted and measured SPECT signals. The model was then used to simulate RNL distributions from a range of catheter placements, resulting in a ratio of the cumulative RNL dose outside versus inside the tumor, the "off-target ratio" (OTR). Optimal catheter placement) was identified by minimizing OTR. RESULTS: Fifteen patients with rGBM from a Phase I/II clinical trial (NCT01906385) were recruited to the study. Our model, with either individual-calibrated or population-assigned parameters, achieved high accuracy (CCC > 0.80) for predicting RNL distributions up to 24 h after delivery. The optimal catheter placements identified using this model achieved a median (range) of 34.56 % (14.70 %-61.12 %) reduction on OTR at the 24 h post-delivery in comparison to the original placements. CONCLUSIONS: Our image-guided model achieved high accuracy for predicting patient-specific RNL distributions and indicates value for optimizing catheter placement for CED of radiolabeled liposomes.

Development and Validation of an Explainable Machine Learning Model for Identification of Hyper-Functioning Parathyroid Glands from High-Frequency Ultrasonographic Images.

OBJECTIVE: To develop and validate a machine learning (ML) model based on high-frequency ultrasound (HFUS) images with the aim to identify the functional status of parathyroid glands (PTGs) in secondary hyper-parathyroidism (SHPT) patients. METHODS: This retrospective study enrolled 60 SHPT patients (27 female, 33 male; mean age: 51.2 years) with 184 PTGs detected from February 2016 to June 2022. All enrollments underwent single-photon emission computed tomography/computed tomography and contrast-enhanced ultrasound examinations. The PTGs were randomly divided into training (n = 147) and testing datasets (n = 37). Four effective ML classifiers were used and combined models incorporating multi-modal HFUS visual signs and radiomics features was constructed based on the optimal classifier. Model performance was compared in terms of discrimination, calibration and clinical utility. The Shapley additive explanation method was used to explain and visualize the main predictors of the optimal model. RESULTS: This model, using a random forest classifier algorithm, outperformed other classifiers. Based on optimal classifier features, the model constructed from ultrasound visual and ML features achieved a favorable performance in the prediction of hyper-functioning PTGs. Compared with the traditional visual model, the ultrasound-based ML model achieved significant (p = 0.03) improvement (area under the curve: 0.859 vs. 0.629) and higher sensitivity (100.0% vs. 94.1%) and accuracy (86.5% vs. 67.6%). Among the predictors attributed to model development, large size and high echogenic heterogeneity of PTGs in ultrasonographic images were more often associated with high risk of hyper-functioning PTGs. CONCLUSION: The ultrasound-based ML model for identifying hyper-functioning PTGs in SHPT patients showed good performance and interpretability using high-frequency ultrasonographic images, which may facilitate clinical management.

Association of dysphagia severity in multiple system atrophy with the specific binding ratio on dopamine transporter SPECT.

OBJECTIVE: Dysphagia in multiple system atrophy (MSA) is life-threatening and is caused by parkinsonism with cerebellar ataxia as a contributing factor. The present study investigated the relationship between dysphagia severity in MSA and the specific binding ratio (SBR) on dopamine transporter (DaT) SPECT using the Hyodo score, a qualitative scale for use with fiberoptic endoscopic evaluation of swallowing (FEES). METHODS: Hyodo score's ability to predict aspiration during a FEES examination of 88 patients with MSA was first tested. Then the clinical characteristics, Hyodo score, and SBR of patients with either predominant parkinsonism (MSA-P; n = 11) or cerebellar ataxia (MSA-C; n = 25) who underwent FEES and DaT SPECT simultaneously were compared. RESULTS: Logistic regression demonstrated that the Hyodo score was a significant predictive factor of aspiration (p = 0.003). The MSA-P group had a significantly higher Hyodo score (p = 0.026) and lower SBR (p = 0.011) than the MSA-C group while neither group demonstrated any significant difference in disease duration at the FEES examination. Linear regression demonstrated a significant, inverse correlation between the Hyodo score and SBR in the MSA-P (p = 0.044; r = -0.616) and MSA-C (p = 0.044; r = -0.406) groups. When the effect of SBR was removed by analysis of covariance, no significant difference in the Hyodo score remained between the groups. CONCLUSIONS: Our results suggested an association between presynaptic changes in nigrostriatal dopaminergic neurons and dysphagia severity in MSA which largely contributes to the difference in dysphagia severity between MSA-P and MSA-C.