Cholinergic changes in Lewy body disease: implications for presentation, progression and subtypes.

Cholinergic degeneration is significant in Lewy body disease, including Parkinson's disease, dementia with Lewy bodies, and isolated REM sleep behaviour disorder. Extensive research has demonstrated cholinergic alterations in the CNS of these disorders. More recently, studies have revealed cholinergic denervation in organs that receive parasympathetic denervation. This enables a comprehensive review of cholinergic changes in Lewy body disease, encompassing both central and peripheral regions, various disease stages and diagnostic categories. Across studies, brain regions affected in Lewy body dementia show equal or greater levels of cholinergic impairment compared to the brain regions affected in Lewy body disease without dementia. This observation suggests a continuum of cholinergic alterations between these disorders. Patients without dementia exhibit relative sparing of limbic regions, whereas occipital and superior temporal regions appear to be affected to a similar extent in patients with and without dementia. This implies that posterior cholinergic cell groups in the basal forebrain are affected in the early stages of Lewy body disorders, while more anterior regions are typically affected later in the disease progression. The topographical changes observed in patients affected by comorbid Alzheimer pathology may reflect a combination of changes seen in pure forms of Lewy body disease and those seen in Alzheimer's disease. This suggests that Alzheimer co-pathology is important to understand cholinergic degeneration in Lewy body disease. Thalamic cholinergic innervation is more affected in Lewy body patients with dementia compared to those without dementia, and this may contribute to the distinct clinical presentations observed in these groups. In patients with Alzheimer's disease, the thalamus is variably affected, suggesting a different sequential involvement of cholinergic cell groups in Alzheimer's disease compared to Lewy body disease. Patients with isolated REM sleep behaviour disorder demonstrate cholinergic denervation in abdominal organs that receive parasympathetic innervation from the dorsal motor nucleus of the vagus, similar to patients who experienced this sleep disorder in their prodrome. This implies that REM sleep behaviour disorder is important for understanding peripheral cholinergic changes in both prodromal and manifest phases of Lewy body disease. In conclusion, cholinergic changes in Lewy body disease carry implications for understanding phenotypes and the influence of Alzheimer co-pathology, delineating subtypes and pathological spreading routes, and for developing tailored treatments targeting the cholinergic system.

Multi-Modality Imaging of Atheromatous Plaques in Peripheral Arterial Disease: Integrating Molecular and Imaging Markers.

Peripheral artery disease (PAD) is a common and debilitating condition characterized by the narrowing of the limb arteries, primarily due to atherosclerosis. Non-invasive multi-modality imaging approaches using computed tomography (CT), magnetic resonance imaging (MRI), and nuclear imaging have emerged as valuable tools for assessing PAD atheromatous plaques and vessel walls. This review provides an overview of these different imaging techniques, their advantages, limitations, and recent advancements. In addition, this review highlights the importance of molecular markers, including those related to inflammation, endothelial dysfunction, and oxidative stress, in PAD pathophysiology. The potential of integrating molecular and imaging markers for an improved understanding of PAD is also discussed. Despite the promise of this integrative approach, there remain several challenges, including technical limitations in imaging modalities and the need for novel molecular marker discovery and validation. Addressing these challenges and embracing future directions in the field will be essential for maximizing the potential of molecular and imaging markers for improving PAD patient outcomes.

Evaluation and Management of Cardiac Sarcoidosis with Advanced Imaging.

A high clinical suspicion in the setting of appropriate history, physical exam, laboratory, and imaging parameters is often required to set the groundwork for diagnosis and management. Echocardiography may show septal thinning, evidence of systolic and diastolic dysfunction, along with impaired global longitudinal strain. Cardiac MRI reveals late gadolinium enhancement along with evidence of myocardial edema and inflammation on T2 weighted imaging and parametric mapping. 18F-FDG PET detects the presence of active inflammation and the presence of scar. Involvement of the right ventricle on MRI or PET confers a high risk for adverse cardiac events and mortality.

High discriminatory ability of peripheral and CFSF biomarkers in Lewy body diseases.

Differential diagnosis between Parkinson's disease (PD) Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), namely spectrum of Lewy bodies disorders (LBDs), may be challenging, and their common underlying pathophysiology is debated. Our aim was to examine relationships among neurodegenerative biomarkers [alpha-synuclein (α-Syn), Alzheimer's Disease (AD)-related (beta-amyloid Aß42, tau [total τΤ and phosphorylated τp-181]), dopaminergic imaging (DATSCAN-SPECT)] and spectrum of LBD. This is a cross-sectional prospective study in 30 PD, 18 PDD, 29 DLB patients and 30 healthy controls. We compared α-Syn in CSF, plasma and serum and CSF Aß42, τΤ and τp-181 across these groups. Correlations between such biomarkers and motor, cognitive/neuropsychiatric tests, and striatal asymmetry indexes were examined. CSF α-Syn was higher in DLB versus PD/PDD/controls, and lower in PD and PDD patients compared to controls (all p < 0.001). Serum α-Syn levels were higher in all patient groups compared to controls. After excluding those DLB patients with CSF AD profile, plasma and serum Syn levels were higher in the LBD group as a whole compared to controls. The combination of CSF α-Syn, serum α-Syn and Aß42 for comparison between PD and DLB [AUC = 0.96 (95% CI 0.90-1.00)] was significantly better when compared to serum α-Syn alone (p < 0.001). Correlation analyses of biomarkers with cognitive/neuropsychiatric scales revealed some associations, but no consistent, cohesive picture. Peripheral biomarkers such as serum α-Syn, and CSF α-Syn and Aß42 may contribute as potential biomarkers to separate LBDs from controls and to differentiate DLB from the other LBDs with high sensitivity and specificity among study groups.

Thromboxane-prostaglandin receptor antagonist, terutroban, prevents neurovascular events after subarachnoid haemorrhage: a nanoSPECT study in rats.

BACKGROUND: Several lipid metabolites in cerebrospinal fluid are correlated with poor outcomes in aneurysmal subarachnoid haemorrhage. Most of these metabolites bind to ubiquitous thromboxane-prostaglandin (TP) receptors, causing vasoconstriction and inflammation. Here, we evaluated terutroban (TBN), a specific TP receptor antagonist, for the prevention of post-haemorrhage blood-brain barrier disruption, neuronal apoptosis and delayed cerebral hypoperfusion. METHODS: The rat double subarachnoid haemorrhage model was produced by twice injecting (days 1 and 2) autologous blood into the cisterna magna. Seventy-eight male Sprague-Dawley rats were assigned to experimental groups. Rats exposed to subarachnoid haemorrhage were allocated to no treatment (SAH group) or TBN treatment by gastric gavage during the first 5 days after haemorrhage (SAH+TBN group). Control rats received artificial cerebrospinal fluid injections (CSF group). Sham-operated rats with or without TBN administration were also studied. Body weight and Garcia neurological scores were assessed on day 2 and day 5. We used nanoscale single-photon emission computed tomography (nanoSPECT) to measure brain uptake of three radiolabelled agents: 99mTechnetium-diethylenetriaminepentacetate (99mTc-DTPA), which indicated blood-brain barrier permeability on day 3, 99mTechnetium-annexin V-128 (99mTc-Anx-V128), which indicated apoptosis on day 4, and 99mTechnetium-hexamethylpropyleneamineoxime (99mTc-HMPAO), which indicated cerebral perfusion on day 5. Basilar artery narrowing was verified histologically, and cerebral TP receptor agonists were quantified. RESULTS: 99mTc-DTPA uptake unveiled blood-brain barrier disruption in the SAH group. TBN mitigated this disruption in the brainstem area. 99mTc-Anx-V128 uptake was increased in the SAH group and TBN diminished this effect in the cerebellum. 99mTc-HMPAO uptake revealed a global decreased perfusion on day 5 in the SAH group that was significantly counteracted by TBN. TBN also mitigated basilar artery vasoconstriction, neurological deficits (on day 2), body weight loss (on day 5) and cerebral production of vasoconstrictors such as Thromboxane B2 and Prostaglandin F2α. CONCLUSIONS: Based on in vivo nanoscale imaging, we demonstrated that TBN protected against blood-brain barrier disruption, exerted an anti-apoptotic effect and improved cerebral perfusion. Thus, TP receptor antagonists showed promising results in treating post-haemorrhage neurovascular events.

Patterns of bone tracer uptake on SPECT-CT in symptomatic and asymptomatic patients with primary total hip arthroplasty.

PURPOSE: The primary purpose of this study was to compare bone tracer uptake (BTU) on SPECT/CT in symptomatic and asymptomatic total hip arthroplasty (THA) and identify a possible relationship between BTU patterns and patient's symptoms. The secondary purpose was to investigate if the fixation methods (cemented versus uncemented) lead to different BTU patterns. METHODS: A total of 58 THAs, 31 symptomatic (group S) and 27 asymptomatic (group AS), were prospectively collected and retrospectively analyzed. All symptomatic patients underwent standardized detailed history, clinical examination, radiographs and 99mTc-HDP SPECT/CT. BTU in SPECT/CT was quantified in three dimensions and anatomically localized in a scheme of quadrants and levels using a customized previously validated software. T tests were used on both quadrants and levels inside and between groups. A Pearson correlation was performed for BTU within the quadrants. An area under receiver operating characteristic curves was drawn in order to find a BTU value that could differentiate the two groups. Within the groups, patients with cemented and uncemented stems were compared for influences on BTU intensity. RESULTS: The causes of pain were identified in 61% of the patients. The most common problem was aseptic loosening (n = 12). In group AS, levels 1, 2 and 5 had similar BTUs. BTUs in these levels were significantly higher than in level 3, 4 and 6. In group S, no significant differences were seen in terms of BTU in level 1-5. However, BTU here was significantly higher than at level 6 (p < 0.001). In both groups, level 1, the superior, had a significantly higher BTU than level 2 (group AS p < 0.01, group S p < 0.05). Comparing the BTU of the two groups among levels, significant differences were found for level 4, level 5 and the entire stem areas (p < 0.05). The ROC curve calculated on the whole stem allowed identification of a BTU ratio of 3.1 that separated the 92.6% patients of group AS with BTU < 3.1 from the 54.8% of patients of group S with a BTU ≥ 3.1. With regards to the fixation technique, only the BTU at the level 6 in group S presented a significant difference between cemented and uncemented stems (p < 0.05). CONCLUSIONS: Higher BTU levels significantly correlated with symptoms, but a normal BTU could not exclude a specific pathology after THA. A threshold of BTU in SPECT/CT was identified to distinguish between symptomatic and asymptomatic patients after THA.

The effectiveness of acupuncture as a treatment for tinnitus: a randomized controlled trial using (99m)Tc-ECD SPECT.

OBJECTIVE: Investigate the effect of acupuncture on brain perfusion using ethyl cysteinate dimer single-photon emission computed tomography ((99m)Tc-ECD SPECT) in patients with tinnitus. METHODS: This randomized, single-blind, sham-control study examined patients (18-60 years old) with normal hearing and chronic, idiopathic, continuous tinnitus. Fifty-seven subjects were randomly assigned to true (n = 30) or sham (n = 27) acupuncture (ACP); (99m)Tc-ECD SPECT examinations were performed before and after 12 twice-weekly ACP sessions. Secondary outcomes included changes in the Tinnitus Handicap Inventory (THI), Visual Analog Scale (VAS), Hamilton Anxiety Scale (HAS) and Beck Depression Inventory (BDI). Imaging data were analysed using Statistical Parametric Mapping (SPM8) software. Regression models were used to examine secondary outcomes via two paradigms: intention-to-treat (ITT; where multiple imputations were conducted because of study attrition) and complete cases. RESULTS: No between-group brain perfusion differences were observed. However, a significant improvement in THI scores was observed at the end of true ACP treatment for all domains (all p values < 0.01) except the catastrophic scale. CONCLUSIONS: ACP might reduce the effects of tinnitus on daily life; however, additional studies should be conducted to verify the effects of ACP on the neural architecture and brain function of tinnitus patients. KEY POINTS: • Efficacy of acupuncture on brain perfusion and symptoms of tinnitus patients. • Acupuncture improved the Tinnitus Handicap Inventory scores in tinnitus patients. • No significant changes in brain perfusion were observed after 12 twice-weekly sessions. • Perfusion changes would reflect changes in neuronal function.

Anterior opercular syndrome induced by Epstein-Barr virus encephalitis.

We report a 19-year-old female presenting with fever, drooling, anarthria, and voluntary facial movement disruption, characteristic of anterior opercular syndrome (AOS). Serological examination revealed Epstein-Barr virus (EBV) infection following acute encephalitis with severe ataxia. A single-photon emission computerized tomography (SPECT) examination indicated hypoperfusion in the left perisylvian region, bilateral thalamus, occipital lobe, and cerebellum. This is the first report of AOS related to EBV encephalitis. SPECT was a useful method for detecting the damaged region of the operculum. In addition, AOS is a clinically distinct entity that may help us understand the mechanisms of language circuits within the operculum.

SPECT Imaging of 2-D and 3-D Distributed Sources with Near-Field Coded Aperture Collimation: Computer Simulation and Real Data Validation.

The imaging of distributed sources with near-field coded aperture (CA) remains extremely challenging and is broadly considered unsuitable for single-photon emission computerized tomography (SPECT). This study proposes a novel CA SPECT reconstruction approach and evaluates the feasibilities of imaging and reconstructing distributed hot sources and cold lesions using near-field CA collimation and iterative image reconstruction. Computer simulations were designed to compare CA and pinhole collimations in two-dimensional radionuclide imaging. Digital phantoms were created and CA images of the phantoms were reconstructed using maximum likelihood expectation maximization (MLEM). Errors and the contrast-to-noise ratio (CNR) were calculated and image resolution was evaluated. An ex vivo rat heart with myocardial infarction was imaged using a micro-SPECT system equipped with a custom-made CA module and a commercial 5-pinhole collimator. Rat CA images were reconstructed via the three-dimensional (3-D) MLEM algorithm developed for CA SPECT with and without correction for a large projection angle, and 5-pinhole images were reconstructed using the commercial software provided by the SPECT system. Phantom images of CA were markedly improved in terms of image quality, quantitative root-mean-squared error, and CNR, as compared to pinhole images. CA and pinhole images yielded similar image resolution, while CA collimation resulted in fewer noise artifacts. CA and pinhole images of the rat heart were well reconstructed and the myocardial perfusion defects could be clearly discerned from 3-D CA and 5-pinhole SPECT images, whereas 5-pinhole SPECT images suffered from severe noise artifacts. Image contrast of CA SPECT was further improved after correction for the large projection angle used in the rat heart imaging. The computer simulations and small-animal imaging study presented herein indicate that the proposed 3-D CA SPECT imaging and reconstruction approaches worked reasonably well, demonstrating the feasibilities of achieving high sensitivity and high resolution SPECT using near-field CA collimation.

Neuroimaging in the differential diagnosis of primary progressive aphasia - illustrative case series in the light of new diagnostic criteria.

BACKGROUND: Primary progressive aphasia (PPA) is a progressive language disorder associated with atrophy of the dominant language hemisphere, typically left. Current PPA criteria divide PPA into three variants: non-fluent (nfvPPA), semantic (svPPA) and logopenic (lvPPA). The classification of PPA into one of the three variants may be performed at 3 levels: I) clinical, II) imaging-supported, III) definite pathologic diagnosis. This paper aimed at assessing the feasibility of the imaging-supported diagnostics of PPA variants in the Polish clinical setting with access to magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) examinations. CASE REPORT: We present the clinical and neuroimaging data on 6 patients (4 women, 2 men) clinically diagnosed with PPA (3 with nfvPPA and 3 with lvPPA) in whom MRI and SPECT were performed in order to determine if imaging-supported diagnosis could be established in those cases. In 4 individuals (2 with nfvPPA and 2 with lvPPA) clinical diagnosis was supported by neuroimaging (SPECT, albeit not MRI), thus level II of PPA diagnosis could be established in those cases. MRI results were either inconsistent with the clinical diagnosis (Patients 1 and 2) or a mixed pattern of atrophy was observed (Patients 3-6). CONCLUSIONS: Imaging-supported diagnosis of PPA variant is more feasible with quantitative analysis of SPECT images than with purely qualitative visual analysis of MRI. Hypoperfusion abnormalities evidenced by SPECT are more variant-specific than patterns of atrophy.

Comparison of perfusion-metabolism mismatch in 99mTc-MIBI and 123I-BMIPP scintigraphy with cardiac magnetic resonance in patients with dilated cardiomyopathy.

BACKGROUND: Cardiac magnetic resonance (CMR) imaging is an established method of detecting myocardial fibrosis related to prognosis in patients with dilated cardiomyopathy (DCM). Recent studies have found that (99m)Tc-methoxy-isobutyl-isonitrile (MIBI) and (123)I-15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) dual single-photon-emission computerized tomography (MIBI-BMIPP dual SPECT) can detect perfusion-metabolism mismatches. We compared MIBI-BMIPP dual SPECT with CMR findings and assessed their prognostic abilities to determine the significance of abnormal metabolism in patients with DCM. METHODS AND RESULTS: Fifty inpatients with DCM (age 58 ± 12 y; 14 female) were assessed with the use of MIBI-BMIPP dual SPECT and CMR. Perfusion-metabolism mismatches were identified mainly at the left ventricular free wall, whereas late gadolinium enhancement (LGE) was evident mostly at the septal wall. During a median follow-up of 33 months, 9 patients developed cardiac events including death, heart failure, and fatal arrhythmia. Event-free survival rates were significantly lower for patients with LGE plus a mismatch than with other abnormalities (P = .001). Among clinical and imaging variables, LGE plus a mismatch was significantly associated with cardiac events (hazard ratio 7.9, 95% confidence interval 1.8-35.6; P = .007). CONCLUSIONS: Coexisting LGE and a perfusion-metabolism mismatch accurately predict future cardiac events in patients with DCM.

Radiochemical and radiobiological assessment of a pyridyl-S-cysteine functionalized bombesin derivative labeled with the (99m)Tc(CO)3(+) core.

Bombesin is a neuropeptide widely studied due to its ability to target various types of cancers. Technetium-99m on the other hand is ideal for diagnostic tumor targeting. The aim of the present study is the investigation of the coupling of the ligand (S)-(2-(2'-pyridyl)ethyl)-d,l-cysteine with the BN-peptide Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met(CONH2) through the spacer aminohexanoic acidand the labeling of the resulting derivative MBN with the synthon [M(CO)3(H2O)3](+) (M=(99m)Tc, Re). The peptide was synthesized according to the SPPS method, purified and characterized by ESI-MS. The new (99m)Tc-labeled biomolecule was stable in vitro, showed high affinity for the human GRP receptor expressed in PC3 cells and the rate of internalization was found to be time-dependent tissue distribution of the radiopeptide was evaluated in normal mice and in prostate cancer experimental models and significant radioactivity uptake was observed in the pancreas of normal mice as well as in PC3 tumors. Dynamic studies of the radiopeptide showed satisfactory tumor images.

99m-Tc TRODAT Single-Photon Emission Computerized Tomography Scan Image Compression using Singular Value Decomposition.

Introduction: The objective of the study was to compress 99m-Tc TRODAT single-photon emission computerized tomography (SPECT) scan image using Singular Value Decomposition (SVD) into an acceptable compressed image and then calculate the compression factor. Materials and Methods: The SVD of every image from the image dataset of 2256 images (of forty-eight 99m-Tc TRODAT SPECT studies [48 studies X 47 trans-axial images = 2256 trans-axial images]) was computed and after truncating singular values smaller than a threshold, the compressed image was reconstructed. The SVD computation time and percentage compression achieved were calculated for each image. Two nuclear medicine physicians visually compared compressed image with its original image, and labeled it as either acceptable or unacceptable. Compressed image having loss of clinical details or presence of compression artifact was labeled unacceptable. The quality of compressed image was also assessed objectively using the following image quality metrics: Error, structural similarity (SSIM), brightness, global contrast factor (GCF), contrast per pixel (CPP), and blur. We also compared the TRODAT uptake in basal ganglia estimated from the compressed image and original image. Results: Nuclear Medicine Physician labeled each image acceptable, as they found compressed image identical to its original image. The values of brightness, GCF, CPP, and blur metrics show that compressed images are less noisy, brighter, and sharper than its original image. The median values of error (0.0006) and SSIM (0.93) indicate that the compressed images were approximately identical to its original image. In 39 out of 48 studies, the percentage difference in TRODAT uptake (in basal ganglia from compressed and original image) was negligible (approximately equal to zero). In remaining 9 studies, the maximum percentage difference was 13%. The SVD computation time and percentage compression achieved for a TRODAT study were 0.17398 s and up to 54.61%, respectively. Conclusions: The compression factor up to 54.61% was achieved during 99m-Tc TRODAT SPECT scan image compression using SVD, for an acceptable compressed image.

Estimating Center of Rotation of Single-Photon Emission Computerized Tomography Projection Images Using MATLAB for Standardization and Calibration.

Objective: The objective of the study was to develop a Personal Computer (PC) based tool to estimate the center of rotation (COR) offsets from COR projection datasets using methods mentioned in IAEA-TECDOC-602. Materials and Methods: Twenty-four COR studies were acquired on Discovery NM 630 Dual head gamma camera fitted with parallel hole collimator, and COR offsets were estimated with the software available at the terminal for processing a COR study. These COR projection images were exported in DICOM. A MATLAB script (software program) was written to estimate COR offset using Method A (using opposite pair of projections) and Method B (using curve fitting method) as mentioned in IAEA-TECDOC-602. Our program read the COR study (in DICOM) and estimated COR offsets using Method A and Method B. The accuracy of the program was verified using simulated projection dataset of a point source object acquired at 6° interval in the range of 0°-360° angle. Bland Altman plot was used for analyzing the agreement between the COR offsets estimated using (1) Method A and Method B mentioned in IAEA-TECDOC-602, and (2) Our program and vendor program available at Discovery NM 630 acquisition terminal. Results: On simulated data, offset from center of gravity (COG) in X direction (COGX) and COG in Y direction (COGY) estimated using Method A was constant (same) at each pair of angles while using Method B, it was found to be in the range (-2 × 10-10, 1 × 10-10) which is negligible. Most of the differences (23 out of 24) between the result of Method A and Method B, and between the results of our program and vendor program was found to be within 95% confidence interval (mean ± 1.96 standard deviation). Conclusions: Our PC-based tool to estimate COR offsets from COR projection datasets using methods mentioned in IAEA-TECDOC-602 was found to be accurate and provides results in agreement with vendor's program. It can be used as an independent tool to estimate COR offset for standardization and calibration purposes.

Nanobody-mediated SPECT/CT imaging reveals the spatiotemporal expression of programmed death-ligand 1 in response to a CD8+ T cell and iNKT cell activating mRNA vaccine.

Rationale: Although promising responses are obtained in patients treated with immune checkpoint inhibitors targeting programmed death ligand 1 (PD-L1) and its receptor programmed death-1 (PD-1), only a fraction of patients benefits from this immunotherapy. Cancer vaccination may be an effective approach to improve the response to immune checkpoint inhibitors anti-PD-L1/PD-1 therapy. However, there is a lack of research on the dynamics of PD-L1 expression in response to cancer vaccination. Methods: We performed non-invasive whole-body imaging to visualize PD-L1 expression at different timepoints after vaccination of melanoma-bearing mice. Mice bearing ovalbumin (OVA) expressing B16 tumors were i.v. injected with the Galsome mRNA vaccine: OVA encoding mRNA lipoplexes co-encapsulating a low or a high dose of the atypical adjuvant α-galactosylceramide (αGC) to activate invariant natural killer T (iNKT) cells. Serial non-invasive whole-body immune imaging was performed using a technetium-99m (99mTc)-labeled anti-PD-L1 nanobody, single-photon emission computerized tomography (SPECT) and X-ray computed tomography (CT) images were quantified. Additionally, cellular expression of PD-L1 was evaluated with flow cytometry. Results: SPECT/CT-imaging showed a rapid and systemic upregulation of PD-L1 after vaccination. PD-L1 expression could not be correlated to the αGC-dose, although we observed a dose-dependent iNKT cell activation. Dynamics of PD-L1 expression were organ-dependent and most pronounced in lungs and liver, organs to which the vaccine was distributed. PD-L1 expression in lungs increased immediately after vaccination and gradually decreased over time, whereas in liver, vaccination-induced PD-L1 upregulation was short-lived. Flow cytometric analysis of these organs further showed myeloid cells as well as non-immune cells with elevated PD-L1 expression in response to vaccination. SPECT/CT imaging of the tumor demonstrated that the expression of PD-L1 remained stable over time and was overall not affected by vaccination although flow cytometric analysis at the cellular level demonstrated changes in PD-L1 expression in various immune cell populations following vaccination. Conclusion: Repeated non-invasive whole-body imaging using 99mTc-labeled anti-PD-L1 nanobodies allows to document the dynamic nature of PD-L1 expression upon vaccination. Galsome vaccination rapidly induced systemic upregulation of PD-L1 expression with the most pronounced upregulation in lungs and liver while flow cytometry analysis showed upregulation of PD-L1 in the tumor microenvironment. This study shows that imaging using nanobodies may be useful for monitoring vaccine-mediated PD-L1 modulation in patients and could provide a rationale for combination therapy. To the best of our knowledge, this is the first report that visualizes PD-L1 expression upon cancer vaccination.

Differentiating Cerebral Toxoplasmosis and Tumor Recurrence by Thallium-201 Single-Photon Emission Computerized Tomography in a 28-Year-Old Female with Astrocytoma.

Cerebral toxoplasmosis is an opportunistic infection that, by itself, is difficult to differentiate from cerebral neoplasms by conventional neuroimaging. It rarely occurs concurrently in patients with a primary brain tumor but when it does, it makes diagnosis and management more difficult. This is a case of a 28-year-old female, diagnosed with a right frontal pleomorphic xanthoastrocytoma with several recurrences, treated with surgery, radiation, and chemotherapy. Three years from diagnosis, the patient was readmitted for generalized body weakness, fever, and a decrease in sensorium. A repeat cranial magnetic resonance imaging showed multiple enhancing lesions in both cerebral hemispheres and in the posterior fossa. Serum toxoplasma IgM and IgG antibody titers were elevated. Single-photon emission computerized tomography (SPECT) with thallium-201 did not show increased tracer uptake in these lesions, favoring toxoplasmosis over tumor recurrence. The patient was treated with trimethoprim-sulfamethoxazole with significant improvement. This is a rare account of cerebral toxoplasmosis arising in the setting of astrocytoma. This is also the first case report to demonstrate the value of thallium-201 SPECT in differentiating central nervous system infection from tumor recurrence, which is pivotal in management. More studies exploring the use of thallium-201 SPECT in distinguishing central nervous system infections from glioma and other malignant tumors should be undertaken to maximize this imaging modality in neuro-oncology practice.

Management and Outcomes of Necrotizing Otitis Externa: A Retrospective Cohort Study in a Tertiary Referral Center.

Objectives: Necrotizing otitis externa (NOE) is a rare infection of the ear that causes osteomyelitis. We aimed to evaluate treatment outcomes and the role of imaging in diagnosing and monitoring disease resolution in a single-center study of patients with NOE. Methods: In this retrospective cohort study, patients with NOE who were diagnosed and treated in a tertiary otology center in Utrecht, The Netherlands, between January 1, 2013 and August 1, 2022, were included. Data were retrieved from the medical records on demographics, symptoms, physical and diagnostic findings, type and duration of treatment, and course of disease. Results: A total of 24 cases were included. Patients were often elderly (mean age = 75 years) and diabetic (88%). Pseudomonas aeruginosa was the most commonly found microorganism (63%). Twenty-two cases (92%) received intravenous antibiotic treatment, and 7 cases (29%) received additional systemic antifungal treatment. The mean duration of systemic treatment was 29 weeks. In 20 out of 22 cases (91%), imaging was used to determine the end point of treatment. None of the cases with a total resolution of disease activity (n = 5) on 18F-fluorodeoxyglucose-positron emission tomography-computed tomography imaging at the time of cessation of therapy showed clinical relapse, compared with 1 out of 4 cases on gallium single-photon emission computerized tomography. Conclusion: Based on the experience from our center, we demonstrated that patients with NOE can successfully be treated with prolonged systemic treatment. Molecular imaging is reasonably successful for disease evaluation and decision-making on the eradication of disease.

Radiometals in Imaging and Therapy: Highlighting Two Decades of Research.

The present article highlights the important progress made in the last two decades in the fields of molecular imaging and radionuclide therapy. Advancements in radiometal-based positron emission tomography, single photon emission computerized tomography, and radionuclide therapy are illustrated in terms of their production routes and ease of radiolabeling. Applications in clinical diagnostic and radionuclide therapy are considered, including human studies under clinical trials; their current stages of clinical translations and findings are summarized. Because the metalloid astatine is used for imaging and radionuclide therapy, it is included in this review. In regard to radionuclide therapy, both beta-minus (ß-) and alpha (α)-emitting radionuclides are discussed by highlighting their production routes, targeted radiopharmaceuticals, and current clinical translation stage.

Modified Algorithm Using Total Count for Calculating Myocardial Washout Rate in Single-Photon Emission Computerized Tomography.

Background: The arithmetic mean of washout rate (WR) (namely, AMWR) of each segment is a commonly used algorithm for calculating WR from a polar map in single-photon emission computerized tomography (SPECT). However, in this algorithm, uneven radiotracer uptake among segments affects WR calculation. To solve this possible issue, we formulated a modified algorithm for calculating WR based on the total count (namely, TCWR). Methods: The WR of iodine-123-ß-methyl-p-iodophenylpentadecanoic acid (BMIPP) was calculated using TCWR and AMWR, and WR values using TCWR and AMWR were compared by disease. Participants included those without cardiovascular diseases (normal), those with CD36 deficiency, triglyceride deposit cardiomyovasculopathy (TGCV), TGCV with old myocardial infarction (OMI), and non-TGCV with OMI. Results: WR values using TCWR and AMWR did not differ significantly in the following groups: normal, 27.4±8.5 and 27.3±8.5% (p=0.97); CD36 deficiency, -3.2±6.5 and -4.1±7.4% (p=0.81); TGCV, 2.4±6.3 and 2.2±6.3% (p=0.93); and TGCV with OMI, -0.9±7.6 and -3.7±8.4% (p=0.32). However, AMWR showed a lower WR than TCWR in non-TGCV with OMI (4.8±8.7 and 18.9±6.7%, p=0.0008). Conclusions: TCWR is suitable for calculating WR using SPECT polar maps even in cases with heterogeneous radiotracer uptake, such as OMIs. TCWR may be applied to measuring the WR of radiopharmaceuticals other than BMIPP in investigating the pathophysiology of heart diseases.

Meningioma grading based on positron emission tomography: A systematic review and meta-analysis.

Introduction: Meningiomas are the most common central nervous system tumor in adults. Knowledge of the tumor grade can guide optimal treatment timing and shape personalized follow-up strategies. Positron emission tomography (PET) has been utilized for the metabolic assessment of various intracranial space-occupying lesions. Herewith, we set out to evaluate the diagnostic accuracy of PET for the noninvasive assessment of meningioma's grade. Materials and methods: The Medline, Scopus and Cochrane databases were systematically searched in March 2022 for studies that evaluated the sensitivity and specificity of PET compared to the gold standard of histological diagnosis in the grading of meningiomas. Summary statistics will be calculated and scatter plots, summary curve from the HSROC model and posterior predictions by empirical Bayes estimates will be presented. Results: Five studies consisting of 242 patients with a total of 196 low-grade (Grade 1) and 46 high grade (Grade 2/3) meningiomas were included in our analysis. Three of the included studies used 18F-FDG, one study used 18F-FLT and one used(Whiting et al., 2011) 18 F-FET as PET tracers. The pooled sensitivity was 76% (95% CI: 52%-91%) and the pooled specificity was 89% (95% CI: 83%-93%). The diagnostic odds ratio was 27.17 (95% CI: 9.22-80.06), the positive likelihood ratio was 7.18 (95% CI: 4.54-11.34) and the negative likelihood ratio was 0.26 (95% CI: 0.11-0.61). Conclusion: PET is a promising and viable option as a noninvasive imaging tool to differentiate the meningioma grades. However, currently it cannot overtake the gold standard of histological grade confirmation. More studies are required for further validation and refinement of this imaging technique and assessment of other radiotracers as well.