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This study investigated a novel radioimmunotherapy strategy for targeting tumor angiogenesis. We developed a radiopharmaceutical complex by labeling an anti-adenosine triphosphate synthase (ATPS) monoclonal antibody (mAb) with the radioisotope 177Lu using DOTA as a chelating agent. 177Lu-DOTA-ATPS mAb demonstrated high labeling efficiency (99.0%) and stability in serum. MKN-45 cancer cells exhibited the highest cellular uptake, which could be specifically blocked by unlabeled ATPS mAb. In mice, 177Lu-DOTA-ATPS mAb accumulated significantly in tumors, with a tumor uptake of 16.0 ± 1.5%ID/g on day 7. 177Lu-DOTA-ATPS mAb treatment significantly reduced the viability of MKN-45 cells in a dose-dependent manner. In a xenograft tumor model, this radioimmunotherapy strategy led to substantial tumor growth inhibition (82.8%). Furthermore, combining 177Lu-DOTA-ATPS mAb with sunitinib, an anti-angiogenic drug, enhanced the therapeutic efficacy of sunitinib in the mouse model. Our study successfully developed 177Lu-DOTA-ATPS mAb, a radioimmunotherapy agent targeting tumor blood vessels. This approach demonstrates significant promise for inhibiting tumor growth, both as a single therapy and in combination with other anti-cancer drugs.
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Objective: White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH's impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes. Methods: Participants aged 49-89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1-2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific. Results: The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males. Discussion: Elderly females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies. Clinical trial registration: The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14.
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INTRODUCTION: This study aimed to explore the potential of whole brain white matter patterns as novel neuroimaging biomarkers for assessing cognitive impairment and disability in older adults. METHODS: We conducted an in-depth analysis of magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans in 454 participants, focusing on white matter patterns and white matter inter-subject variability (WM-ISV). RESULTS: The white matter pattern ensemble model, combining MRI and amyloid PET, demonstrated a significantly higher classification performance for cognitive impairment and disability. Participants with Alzheimer's disease (AD) exhibited higher WM-ISV than participants with subjective cognitive decline, mild cognitive impairment, and vascular dementia. Furthermore, WM-ISV correlated significantly with blood-based biomarkers (such as glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]), and cognitive function and disability scores. DISCUSSION: Our results suggest that white matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making and determining cognitive impairment and disability. HIGHLIGHTS: The ensemble model combined both magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) and demonstrated a significantly higher classification performance for cognitive impairment and disability. Alzheimer's disease (AD) revealed a notably higher heterogeneity compared to that in subjective cognitive decline, mild cognitive impairment, or vascular dementia. White matter inter-subject variability (WM-ISV) was significantly correlated with blood-based biomarkers (glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]) and with the polygenic risk score for AD. White matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making processes and determining cognitive impairment and disability.
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PURPOSE: We aimed to develop deep learning (DL)-based attenuation correction models for Tl-201 myocardial perfusion SPECT (MPS) images and evaluate their clinical feasibility. PATIENTS AND METHODS: We conducted a retrospective study of patients with suspected or known coronary artery disease. We proposed a DL-based image-to-image translation technique to transform non-attenuation-corrected images into CT-based attenuation-corrected (CT AC ) images. The model was trained using a modified U-Net with structural similarity index (SSIM) loss and mean squared error (MSE) loss and compared with other models. Segment-wise analysis using a polar map and visual assessment for the generated attenuation-corrected (GEN AC ) images were also performed to evaluate clinical feasibility. RESULTS: This study comprised 657 men and 328 women (age, 65 ± 11 years). Among the various models, the modified U-Net achieved the highest performance with an average mean absolute error of 0.003, an SSIM of 0.990, and a peak signal-to-noise ratio of 33.658. The performance of the model was not different between the stress and rest datasets. In the segment-wise analysis, the myocardial perfusion of the inferior wall was significantly higher in GEN AC images than in the non-attenuation-corrected images in both the rest and stress test sets ( P < 0.05). In the visual assessment of patients with diaphragmatic attenuation, scores of 4 (similar to CT AC images) or 5 (indistinguishable from CT AC images) were assigned to most GEN AC images (65/68). CONCLUSIONS: Our clinically feasible DL-based attenuation correction models can replace the CT-based method in Tl-201 MPS, and it would be useful in case SPECT/CT is unavailable for MPS.
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Aprendizaje Profundo , Radioisótopos de Talio , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Estudios de Factibilidad , Sensibilidad y Especificidad , Tomografía Computarizada de Emisión de Fotón Único/métodos , Perfusión , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
White matter hyperintensity (WMH) lesions on brain MRI images are surrogate markers of cerebral small vessel disease. Longitudinal studies examining the association between diabetes and WMH progression have yielded mixed results. Thus, in this study, we investigated the association between HbA1c, a biomarker for the presence and severity of hyperglycemia, and longitudinal WMH change after adjusting for known risk factors for WMH progression. We recruited 64 participants from South Korean memory clinics to undergo brain MRI at the baseline and a 2-year follow-up. We found the following. First, higher HbA1c was associated with greater global WMH volume (WMHV) changes after adjusting for known risk factors (ß = 7.7 × 10-4; P = 0.025). Second, the association between baseline WMHV and WMHV progression was only significant at diabetic levels of HbA1c (P < 0.05, when HbA1c >6.51%), and non-apolipoprotein E (APOE) ε4 carriers had a stronger association between HbA1c and WMHV progression (ß = -2.59 × 10-3; P = 0.004). Third, associations of WMHV progression with HbA1c were particularly apparent for deep WMHV change (ß = 7.17 × 10-4; P < 0.01) compared with periventricular WMHV change and, for frontal (ß = 5.00 × 10-4; P < 0.001) and parietal (ß = 1.53 × 10-4; P < 0.05) lobes, WMHV change compared with occipital and temporal WMHV change. In conclusion, higher HbA1c levels were associated with greater 2-year WMHV progression, especially in non-APOE ε4 participants or those with diabetic levels of HbA1c. These findings demonstrate that diabetes may potentially exacerbate cerebrovascular and white matter disease.
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Diabetes Mellitus , Sustancia Blanca , Humanos , Hemoglobina Glucada , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Imagen por Resonancia Magnética/métodos , Estudios Longitudinales , Biomarcadores , Diabetes Mellitus/patologíaRESUMEN
BACKGROUND: Corticobasal syndrome (CBS) is a neurodegeneration characterized by asymmetric parkinsonism, dystonia, myoclonus, and apraxia. In the early stage, CBS presents with asymmetric parkinsonism and cortical symptoms (apraxia and alien hand), and neuroimaging finding is often vague, making early clinical differentiation from idiopathic Parkinson disease (IPD) challenging. This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter (DAT) uptake using dual-phase FP-CIT PET in discriminating between CBS and IPD at early stage. PATIENTS AND METHODS: The study enrolled clinically diagnosed CBS (n = 11) and IPD (n = 22) patients (age and sex matched). All participants underwent dual-phase 18 F-FP-CIT PET, and regional SUV ratio (SUVR) was obtained by semiquantitative analysis. The early perfusion imaging and DAT imaging were compared between groups. RESULTS: The regional SUVRs (early phase) of the frontal lobe, thalamus, cingulate, and caudate were significantly lower in patients with CBS, whereas the SUVR of occipital lobe was lower in the IPD group. The CBS group exhibited more prominent asymmetry than the IPD group, particularly in the perirolandic area, superior frontal gyrus, and anterior parietal lobe in early phase PET. Striatal DAT uptake (delayed phase) revealed that the caudate showed lower SUVR and prominent asymmetry in the CBS group, and the caudate-to-putamen ratio (CP ratio) was significantly lower in CBS patients ( P < 0.001). Among the parameters (early and delayed), the CP ratio in DAT exhibited the most powerful discriminative power from receiver operating characteristic curve comparison (area under curve = 0.983). CONCLUSIONS: This study demonstrated that the dual-phase FP-CIT PET is useful in differentiating CBS and IPD in the early stage of the disease, and a lower CP ratio of DAT imaging is highly informative for distinguishing between corticobasal degeneration and IPD.
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Apraxias , Degeneración Corticobasal , Enfermedad de Parkinson , Trastornos Parkinsonianos , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Tropanos , Tomografía de Emisión de Positrones/métodos , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Diagnóstico PrecozRESUMEN
ABSTRACT: A 76-year-old woman with a history of diabetes mellitus presented with right-side dominant generalized chorea. At presentation, her blood glucose level was 500 mg/dL with an HbA1C of 11%. Because the patient had been on levodopa treatment from her primary physician, a dual-phase 18F-FP-CIT PET scan was performed. The early-phase images showed increased perfusion in the bilateral striatum, and the delayed-phase images revealed decreased uptake in the left caudate. Hyperperfusion in the striatum may indicate the acute phase of hyperglycemic chorea. This image illustrates the advantage of adding early-phase scans in 18F-FP-CIT PET in differentiating various hyperkinetic and hypokinetic disorders.
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Corea , Femenino , Humanos , Anciano , Corea/diagnóstico por imagen , Cuerpo Estriado/diagnóstico por imagen , Neostriado , Tomografía de Emisión de PositronesRESUMEN
Several programs are widely used for clinical and research purposes to automatically quantify the degree of amyloid deposition in the brain using positron emission tomography (PET) images. Given that very few studies have investigated the use of Heuron, a PET image quantification software approved for clinical use, this study aimed to compare amyloid deposition values quantified from 18F-flutemetamol PET images using PMOD and Heuron. Amyloid PET data obtained from 408 patients were analysed using each quantitative program; moreover, the standardized uptake value ratios (SUVRs) of target areas were obtained by dividing the standardized uptake value (SUV) of the target region by the SUV of cerebellar grey matter as a reference. Compared with PMOD, Heuron yielded significantly higher SUVRs for all target areas (paired sample t-test, p < 0.001), except for the PC/PCC (p = 0.986). However, the Bland-Altman plot analysis indicated that the two quantitative methods may be used interchangeably. Moreover, receiver operating characteristic curve analysis revealed no significant between-method difference in the performance of the SUVRs in evaluating the visual positivity of amyloid deposits (p = 0.948). In conclusion, Heuron and PMOD have comparable performance in quantifying the degree of amyloid deposits in PET images.
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Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Placa Amiloide , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Tomografía de Emisión de Positrones/métodos , Curva ROC , Amiloide/metabolismo , Proteínas Amiloidogénicas , Compuestos de Anilina , Péptidos beta-Amiloides/metabolismoRESUMEN
BACKGROUND: Isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD) is considered as a prodromal stage of either multiple system atrophy (MSA) or Lewy body disease (LBD; Parkinson's disease and dementia with Lewy bodies). However, current knowledge is limited in predicting and differentiating the type of future phenoconversion in iRBD patients. We investigated the role of plasma neurofilament light chain (NfL) and cardiac metaiodobenzylguanidine (MIBG) uptake as predictors for phenoconversion. METHODS: Forty patients with iRBD were enrolled between April 2018 and October 2019 and prospectively followed every 3 months to determine phenoconversion to either MSA or LBD. Plasma NfL levels were measured at enrollment. Cardiac MIBG uptake and striatal dopamine transporter uptake were assessed at baseline. RESULTS: Patients were followed for a median of 2.92 years. Four patients converted to MSA and 7 to LBD. Plasma NfL level at baseline was significantly higher in future MSA-converters (median 23.2 pg/mL) when compared with the rest of the samples (median 14.1 pg/mL, p = 0.003). NfL level above 21.3 pg/mL predicted phenoconversion to MSA with the sensitivity of 100% and specificity of 94.3%. Baseline MIBG heart-to-mediastinum ratio of LBD-converters (median 1.10) was significantly lower when compared with the rest (median 2.00, p < 0.001). Heart-to-mediastinum ratio below 1.545 predicted phenoconversion to LBD with the sensitivity of 100% and specificity of 92.9%. CONCLUSIONS: Plasma NfL and cardiac MIBG uptake may be useful biomarkers in predicting phenoconversion of iRBD. Elevated plasma NfL levels may suggest imminent phenoconversion to MSA, whereas low cardiac MIBG uptake suggests phenoconversion to LBD.
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Enfermedad por Cuerpos de Lewy , Atrofia de Múltiples Sistemas , Enfermedad de Parkinson , Trastorno de la Conducta del Sueño REM , Humanos , 3-Yodobencilguanidina , Trastorno de la Conducta del Sueño REM/diagnóstico por imagen , Filamentos Intermedios , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Atrofia de Múltiples Sistemas/diagnóstico por imagenRESUMEN
This study was conducted to investigate the effects of thyroid hormone withdrawal (THW) and recombinant human thyroid-stimulating hormone (rhTSH) administration on renal function in patients with thyroid cancer after total thyroidectomy. This study included 202 patients who discontinued thyroid hormone therapy and/or received rhTSH after total thyroidectomy. Creatinine (Cr), blood urea nitrogen (BUN) levels, and estimated glomerular filtration rate (eGFR) were assessed at the following three time points: before thyroidectomy, at least 3 weeks after THW, and 1 day after the second injection of rhTSH. The median serum Cr level was significantly higher following THW compared to that before thyroidectomy (0.95 versus 0.70). In contrast, the median BUN level was significantly lower after THW compared to that before thyroidectomy (9.8 versus 11.3). Over a fifth (22.2%) of patients had abnormal eGFR values after THW, which was significantly greater than that before thyroidectomy. In contrast, renal parameter values after rhTSH administration were not significantly different than those before thyroidectomy. In conclusion, THW affects renal function in patients with thyroid cancer who have undergone total thyroidectomy. However, renal function in such patients is not affected by rhTSH administration.
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Neoplasias de la Tiroides , Tirotropina Alfa , Humanos , Tirotropina , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/cirugía , Hormonas Tiroideas , Riñón/fisiología , Proteínas Recombinantes/uso terapéuticoRESUMEN
BACKGROUND AND PURPOSE: Parkinson's disease (PD) with glucocerebrosidase (GBA) gene mutation (GBA-PD) is known to show more rapid clinical progression than sporadic PD without GBA mutation (sPD). This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter uptake and cardiac meta-iodobenzylguanidine (MIBG) uptake of GBA-PD in comparison to sPD. METHODS: Through next-generation sequencing analysis targeting 41 genes, a total of 16 GBA-PD and 24 sPD patients (sex, age matched) were enrolled in the study, and the clinical, dual-phase [18 F]-N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane (1 8 F-FP-CIT) positron emission tomography (PET) and cardiac 123 I-MIBG scintigraphy results were compared between the two groups. RESULTS: The GBA-PD group had higher rates of rapid eye movement sleep behavior disorder, orthostatic hypotension and neuropsychiatric symptoms than the sPD group. Early-phase 18 F-FP-CIT PET showed significantly lower standard uptake value ratio on bilateral posterior parietal cortex (0.94 ± 0.05 vs. 1.02 ± 0.04, p = 0.011) and part of the occipital cortex (p < 0.05) in the GBA-PD group than the sPD group. In striatal dopamine transporter uptake, the regional standard uptake value ratio, asymmetry index and caudate-to-putamen ratio were similar between the two groups. The GBA-PD group had a lower heart-to-mediastinum uptake ratio in 123 I-MIBG scintigraphy than the sPD group. CONCLUSIONS: The GBA-PD patients showed decreased regional perfusion in the bilateral posterior parietal and occipital cortex. Cardiac sympathetic denervation and non-motor symptoms (orthostatic hypotension, rapid eye movement sleep behavior disorder) were more common in GBA-PD than sPD. These findings suggest that GBA-PD patients have more widespread peripheral (extranigral) α-synuclein accumulation, representing a body-first PD subtype.
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Hipotensión Ortostática , Enfermedad de Parkinson , Trastorno de la Conducta del Sueño REM , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/genética , 3-Yodobencilguanidina , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Glucosilceramidasa/genética , Tomografía Computarizada de Emisión de Fotón Único/métodos , Tomografía de Emisión de Positrones , Tropanos , Cintigrafía , MutaciónRESUMEN
Central post-stroke pain (CPSP) is an intractable neuropathic pain that can occur following central nervous system injuries. Spino-thalamo-cortical pathway damage contributes to CPSP development. However, brain regions involved in CPSP are unknown and previous studies were limited to supratentorial strokes with cortical lesion involvement. We analyzed the brain metabolism changes associated with CPSP following pontine hemorrhage. Thirty-two patients with isolated pontine hemorrhage were examined; 14 had CPSP, while 18 did not. Brain glucose metabolism was evaluated using 18F-fluorodeoxyglucose-positron emission tomography images. Additionally, regions revealing metabolic correlation with CPSP severity were analyzed. Patients with CPSP showed changes in the brain metabolism in the cerebral cortices and cerebellum. Compared with the control group, the CPSP group showed significant hypometabolism in the contralesional rostral anterior cingulum and ipsilesional primary motor cortex (Puncorrected < 0.001). However, increased brain metabolism was observed in the ipsilesional cerebellum (VI) and contralesional cerebellum (lobule VIIB) (Puncorrected < 0.001). Moreover, increased pain intensity correlated with decreased metabolism in the ipsilesional supplementary motor area and contralesional angular gyrus. This study emphasizes the role of the many different areas of the cortex that are involved in affective and cognitive processing in the development of CPSP.
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OBJECTIVES: Our aim was to evaluate the association between salivary gland scintigraphy and the clinical parameters, including histological characteristics of salivary glands, in patients with primary Sjogren's syndrome (pSS). METHODS: Forty-one pSS patients were included in the study. The patients who had received salivary gland scintigraphy and minor salivary gland biopsy were retrospectively analyzed. Salivary gland scintigraphy was interpreted via semi-quantitative methods obtained by calculating the peak uptake and washout of each gland using regions of interest. All specimens were examined by pathologists for focus scores and leukocyte common antigen (LCA) to determine the degree of inflammatory infiltration. RESULTS: The mean age of pSS patients was 46.4 years, 82.9% were female, and the mean duration of symptoms was 2.5 years. The focus score was negatively correlated to the mean peak uptake (r = â0.396; p = 0.019), mean uptake (r = â0.388; p = 0.021), and mean percentage washout (r = â0.391; p = 0.02). In addition, the focus score and number of LCA positive cells per mm2 were correlated with the clinical parameters including erythrocyte sedimentation rate, globulin, rheumatoid factor, unstimulated whole saliva, and stimulated whole saliva flow. The number of LCA positive cells per mm2 was negatively correlated to leukocytes and hemoglobin. CONCLUSION: Although the diagnostic role of salivary gland biopsy is widely accepted and features in the classification criteria of Sjogren's syndrome, salivary gland scintigraphy may be an acceptable alternative method especially if a non-invasive test is required.
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Síndrome de Sjögren , Femenino , Humanos , Antígenos Comunes de Leucocito , Masculino , Persona de Mediana Edad , Cintigrafía , Estudios Retrospectivos , Factor Reumatoide , Glándulas Salivales/diagnóstico por imagen , Glándulas Salivales/patología , Glándulas Salivales Menores/diagnóstico por imagen , Glándulas Salivales Menores/patología , Síndrome de Sjögren/diagnósticoRESUMEN
ABSTRACT: Early diagnosis of Creutzfeldt-Jakob disease (CJD) patients is often challenging due to the low sensitivity of the current clinical diagnostic criteria. We describe MRI and dual-phase 18 F-FP-CIT PET findings in 2 cases of sporadic CJD presenting different clinical phenotypes (Heidenhain variant and corticobasal syndrome). Our case series suggest that dual-phase FP-CIT-PET findings may improve the diagnosis of CJD by combining the perfusion patterns in early phase with the dopamine transporter density in delayed phase. Familiarity with these dual-phase FP-CIT PET findings is helpful for early correct diagnosis of CJD.
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Síndrome de Creutzfeldt-Jakob , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagen , Diagnóstico Diferencial , Humanos , Fenotipo , Tomografía de Emisión de Positrones , TropanosRESUMEN
ABSTRACT: The major salivary glands, namely, the parotid, submandibular, and sublingual glands, are important in maintaining oral cavity health. A salivary gland scan is used to evaluate the uptake and excretory function of the salivary glands. By intravenously injecting 99m TcO 4- , which is distributed like chloride ions in the body, the glands become visible on the salivary gland scan. The parotid and submandibular glands are typically appreciated on the salivary gland scan, but the sublingual gland is not. We present a rare image of a prominent sublingual gland on a salivary gland scan.
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Glándulas Salivales , Glándula Sublingual , Humanos , Glándula Parótida/diagnóstico por imagen , Cintigrafía , Glándulas Salivales/diagnóstico por imagen , Glándula Sublingual/diagnóstico por imagen , Glándula Submandibular/diagnóstico por imagenRESUMEN
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome involving an uncontrolled immune response with variable triggers. HLH is rare but highly fatal, even with proper treatment; therefore, early recognition and diagnosis are crucial for management. Although the role of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in HLH is poorly defined, it can provide valuable information on disease status and possible triggers. Herein, we report an F-18 FDG PET/CT study on a case of NK/T-cell lymphoma that progressed from Epstein-Barr virus-associated HLH.
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OBJECTIVE: We aimed to present the study design and baseline cross-sectional participant characteristics of biobank innovations for chronic cerebrovascular disease with Alzheimer's disease study (BICWALZS) participants. METHODS: A total of 1,013 participants were enrolled in BICWALZS from October 2016 to December 2020. All participants underwent clinical assessments, basic blood tests, and standardized neuropsychological tests (n=1,013). We performed brain magnetic resonance imaging (MRI, n=817), brain amyloid positron emission tomography (PET, n=713), single nucleotide polymorphism microarray chip (K-Chip, n=949), locomotor activity assessment (actigraphy, n=200), and patient-derived dermal fibroblast sampling (n=175) on a subset of participants. RESULTS: The mean age was 72.8 years, and 658 (65.0%) were females. Based on clinical assessments, total of 168, 534, 211, 80, and 20 had subjective cognitive decline, mild cognitive impairment (MCI), Alzheimer's dementia, vascular dementia, and other types of dementia or not otherwise specified, respectively. Based on neuroimaging biomarkers and cognition, 199, 159, 78, and 204 were cognitively normal (CN), Alzheimer's disease (AD)-related cognitive impairment, vascular cognitive impairment, and not otherwise specified due to mixed pathology (NOS). Each group exhibited many differences in various clinical, neuropsychological, and neuroimaging results at baseline. Baseline characteristics of BICWALZS participants in the MCI, AD, and vascular dementia groups were generally acceptable and consistent with 26 worldwide dementia cohorts and another independent AD cohort in Korea. CONCLUSION: The BICWALZS is a prospective and longitudinal study assessing various clinical and biomarker characteristics in older adults with cognitive complaints. Details of the recruitment process, methodology, and baseline assessment results are described in this paper.
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Cardiac 123I-metaiodobenzylguanidine (MIBG) uptake correlates with the extent of cardiac sympathetic denervation found in disease with Lewy pathology, such as Parkinson's disease (PD). Protein α-synuclein, the main component of Lewy body, is a candidate biomarker of PD, but its relationship with cardiac MIBG uptake has never been explored. Plasma α-synuclein levels were measured in 37 patients with early PD. Cardiac 123I-MIBG scintigraphy and 18F-FP-CIT brain PET were performed, and striatal dopamine transporter (DAT) uptake was quantified using automated segmentation. The relationships of plasma α-synuclein levels with cardiac MIBG and striatal DAT uptake were investigated. The plasma α-synuclein level correlated with early (R = 0.38, P = 0.033) and delayed (R = 0.49, P = 0.0055) MIBG heart-to-mediastinum (H/M) ratios, and its correlation with delayed H/M ratio remained significant after adjustment with age, disease duration, motor severity, and striatal DAT uptake (P = 0.016). The regional SUVRs of any subregions of caudate and putamen did not correlate with plasma α-synuclein level. In the patients with early PD, the plasma α-synuclein level correlated with cardiac sympathetic denervation, but not with nigrostriatal degeneration. This may suggest that plasma α-synuclein levels more readily reflect the peripheral deposition of Lewy bodies than their central deposition.
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3-Yodobencilguanidina/farmacología , Encéfalo/diagnóstico por imagen , Corazón/diagnóstico por imagen , Enfermedad de Parkinson/diagnóstico por imagen , Radiofármacos/farmacología , alfa-Sinucleína/sangre , Anciano , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/sangre , Tomografía de Emisión de Positrones , Cintigrafía , Tropanos/farmacocinéticaRESUMEN
PURPOSE: The purpose of this study was to determine the lowest Tl-201 dose that does not reduce the image quality of myocardial perfusion SPECT (MPS) by Poisson resampling simulation. METHODS: One hundred and twelve consecutive MPS data from patients with suspected or known coronary artery disease were collected retrospectively. Stress and rest MPS data were resampled using the Poisson method with 33%, 50%, 67%, and 100% count settings. Two nuclear medicine physicians assessed the image quality of reconstructed data visually by giving grades from - 2 to + 2. The summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) were obtained on the workstation. Image quality grades and semi-quantitative scores were then compared among these resampled images. RESULTS: The proportions of "adequate" image quality were 0.48, 0.75, 0.92, and 0.96 for the groups of images with 33%, 50%, 67%, and 100% data, respectively. The quality of the resampled images was significantly degraded at 50% and 33% count settings, while the image quality was not different between 67 and 100% count settings. We also found that high body mass index further decreased image quality at 33% count setting. Among the semi-quantitative parameters, SSS and SRS showed a tendency to increase with a decline in count. CONCLUSION: Based on the simulation results, Tl-201 dose for MPS can be reduced to 74 MBq without significant loss of image quality. However, the SSS and SRS can be changed significantly, and it needs to be further verified under the different conditions.
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To delineate the impact of non-motor markers (REM sleep behavior disorder (RBD), orthostatic hypotension (OH), cardiac sympathetic denervation, hyposmia) on neuronal injury in early-stage Parkinson's disease (PD), we measured the plasma neurofilament light chain (NFL) level of PD patients and evaluated its relationship with these markers. The study population comprised a cohort of 77 patients with PD and 54 controls. OH was assessed using 5-min head-up tilt-table test. Other clinical parameters such as RBD, Unified Parkinson's Disease Rating Scale (UPDRS), cognition, Cross-Cultural Smell Identification Test (CCSIT), white matter hyperintensity (WMH), cardiac metaiodobenzylguanidine (MIBG) and striatal dopamine transporter (DAT) uptake were assessed. Plasma NFL levels were measured using Simoa platform. During mean 24.8 months of follow-up, 70 patients remained PD, 5 patients converted to Parkinson-plus syndrome (P + converter), and 2 were lost to follow-up. NFL level did not differ between PD and control groups (age-adjusted means 10.40 pg/mL vs 9.51 pg/mL, p = 0.151), but PD patients with OH (median 15.31 pg/mL) had higher levels compared with those without OH (median 9.2 pg/mL, p = 0.008), as well as the control group (median 9.7 pg/mL, p = 0.002). P + converter group had the highest plasma NFL level (38.17 pg/mL, p < 0.001). In a multiple regression analysis, OH, age, and disease duration independently correlated with plasma NFL level. This finding adds biomarker-based evidence for poor clinical outcomes associated with OH in patients with PD.