Rapidly growing distal choroidal artery aneurysm re-rupture following revascularization for hemorrhagic Moyamoya disease: A case report.

Intracranial hemorrhage is the leading cause of neurological deficits and poor prognosis in adult patients with Moyamoya disease (MMD). Intracranial hemorrhage is occasionally accompanied by MMD-associated aneurysm and requires additional treatment. To date, direct or indirect bypass surgery or endovascular treatment, such as coil embolization, has been adopted and has achieved successful outcomes. The rapid growth of MMD-associated aneurysms and rebleeding after direct bypass surgery via superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis has rarely been reported. We report a case of a rapidly growing fragile arterial pseudoaneurysm in a patient with MMD. A 45-year-old female was admitted with a headache and decreased mental status. Radiological evaluation, including distal subtraction angiography, revealed intraventricular hemorrhage with a left posterior choroidal artery pseudoaneurysm. Within 4 days after revascularization surgery via STA-MCA direct bypass, the size of the pseudoaneurysm rapidly increased and rebleeding occurred, requiring coil embolization. After endovascular therapy and a second STA-MCA bypass surgery, the patient recovered well and was discharged 8 days later. Follow-up radiological imaging revealed an obliterated pseudoaneurysm without rebleeding or complications. In this case, the rapid growth of an MMD-associated pseudoaneurysm was observed after revascularization surgery because of temporary hemodynamic instability. This report raises questions regarding the causes and management of unstable postbypass hemodynamics.

Targeted deletion of CD244 on monocytes promotes differentiation into anti-tumorigenic macrophages and potentiates PD-L1 blockade in melanoma.

BACKGROUND: In the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244. METHODS: To directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific CD244-deficient mice were generated using cre-lox recombination and challenged with B16F10 melanoma. The phenotype and function of tumor-infiltrating macrophages along with antigen-specific CD8 T cells were analyzed by flow cytometry and single cell RNA sequencing data analysis, and the molecular mechanism underlying anti-tumorigenic macrophage differentiation, antigen presentation, phagocytosis was investigated ex vivo. Finally, the clinical feasibility of CD244-negative monocytes as a therapeutic modality in melanoma was confirmed by adoptive transfer experiments. RESULTS: CD244fl/flLysMcre mice demonstrated a significant reduction in tumor volume (61% relative to that of the CD244fl/fl control group) 14 days after tumor implantation. Within tumor mass, CD244fl/flLysMcre mice also showed higher percentages of Ly6Clow macrophages, along with elevated gp100+IFN-γ+ CD8 T cells. Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Combining anti-PD-L1 antibody with CD244-/- bone marrow-derived macrophages markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with wild-type macrophages. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset revealed close association between CD244 and the inhibition of macrophage maturation and function. Furthermore, the presence of CD244-negative monocytes/macrophages significantly increased patient survival in primary and metastatic tumors. CONCLUSION: Our study highlights the novel role of CD244 on monocytes/macrophages in restraining anti-tumorigenic macrophage generation and tumor antigen-specific T cell response in melanoma. Importantly, our findings suggest that CD244-deficient macrophages could potentially be used as a therapeutic agent in combination with immune checkpoint inhibitors. Furthermore, CD244 expression in monocyte-lineage cells serve as a prognostic marker in cancer patients.

Morphologic differences between ruptured and unruptured choroidal anastomosis in adult moyamoya disease: a high-resolution vessel wall imaging study.

OBJECTIVE: Choroidal anastomosis (ChA) has been implicated as the main indicator of an increased hemorrhagic risk in adult moyamoya disease. In this retrospective study, the authors aimed to identify the potential risk factors that can influence the rupture of ChA. METHODS: The authors evaluated the clinical and radiological data on brain hemispheres positive for ChA from September 2019 to March 2023. The rupture status of the ChA was determined using previously described methods. Two independent raters quantitatively investigated the lumen diameter (LD) and lumen area (LA) of the ChA using high-resolution vessel wall imaging (VWI). Multivariate logistic regression analysis was conducted to identify the risk factors for ruptured ChA. RESULTS: Ruptured and unruptured ChAs were identified in 16 and 60 hemispheres, respectively. Univariate analysis showed that the mean values of the LD (1.251 ± 0.241 vs 0.967 ± 0.214 mm, p < 0.001) and LA (1.607 ± 0.445 vs 0.945 ± 0.372 mm2, p < 0.001) of ChAs were significantly greater in the ruptured group than in the unruptured group. A periventricular anastomosis (PA) score of 1, indicating the angiographic presence of ChA alone, was more prevalent in the ruptured group than in the unruptured group (43.8% vs 11.7%, p = 0.003). Multivariate analysis demonstrated that a larger LA of the ChA (OR 37.01, 95% CI 5.787-236.7, p < 0.001) and PA score 1 (OR 6.661, 95% CI 1.260-35.21, p = 0.026) were independently associated with ruptured ChA hemispheres. Receiver operating characteristic curve analysis revealed that the optimal cutoff point for the LA was 1.285 mm2 (sensitivity 81.3%, specificity 86.7%). CONCLUSIONS: A larger LA (> 1.285 mm2) of the ChA and the angiographic presence of ChA alone are independent risk factors for a ruptured ChA. Revascularization surgery for the prevention of future hemorrhage may be indicated for hemispheres with a high-risk unruptured ChA. These characteristics may help to determine treatment strategies for patients with an unruptured ChA.

Dural tail sign positive tumors: Points to make a differential diagnosis.

Representative patients were treated with total surgical mass resection, and each tumor was histopathologically confirmed to have a secretory meningioma, intradural metastasis of gynecologic origin, and dural metastasis of lung origin. The imaging findings of these patients were inconclusive in differentiating meningioma from metastasis; hence, advanced magnetic resonance imaging (MRI) techniques were considered. Based on these reports, we studied how to differentiate typical meningiomas from atypical and malignant meningiomas and other dura-based malignant tumors using conventional computed tomography and MRI.

Deep-learning model for diagnostic clue: detecting the dural tail sign for meningiomas on contrast-enhanced T1 weighted images.

Background: Meningiomas are the most common primary central nervous system tumors, and magnetic resonance imaging (MRI), especially contrast-enhanced T1 weighted image (CE T1WI), is used as a fundamental imaging modality for the detection and analysis of the tumors. In this study, we propose an automated deep-learning model for meningioma detection using the dural tail sign. Methods: The dataset included 123 patients with 3,824 dural tail signs on sagittal CE T1WI. The dataset was divided into training and test datasets based on specific time point, and 78 and 45 patients were comprised for the training and test dataset, respectively. To compensate for the small sample size of the training dataset, 39 additional patients with 69 dural tail signs from the open dataset were appended to the training dataset. A You Only Look Once (YOLO) v4 network was trained with sagittal CE T1WI to detect dural tail signs. The normal group dataset, comprised of 51 patients with no abnormal finding on MRI, was employed to evaluate the specificity of the trained model. Results: The sensitivity and false positive average were 82.22% and 29.73, respectively, in the test dataset. The specificity and false positive average were 17.65% and 3.16, respectively, in the normal dataset. Most of the false-positive cases in the test dataset were enhancing vessels, misinterpreted as dural thickening. Conclusions: The proposed model demonstrates an automated detection system for the dural tail sign to identify meningioma in general screening MRI. Our model can facilitate and alleviate radiologists' reading process by notifying the possibility of incidental dural mass based on dural tail sign detection.

Suppression of the antitumoral activity of natural killer cells under indirect coculture with cancer-associated fibroblasts in a pancreatic TIME-on-chip model.

BACKGROUND: Recently, natural killer (NK) cells emerged as a treatment option for various solid tumors. However, the immunosuppressive tumor immune microenvironment (TIME) can reduce the cytotoxic ability of NK cells in pancreatic ductal adenocarcinoma. Cancer-associated fibroblasts within the tumor stroma can suppress immune surveillance by dysregulating factors involved in the cellular activity of NK cells. Herein, the effect of activated pancreatic stellate cells (aPSCs) on NK cell-mediated anticancer efficacy under three-dimensional (3D) coculture conditions was investigated. METHODS: 3D cocultures of PANC-1 tumor spheroids (TSs) with aPSCs and NK-92 cells in a collagen matrix were optimized to identify the occurring cellular interactions and differential cytokine profiles in conditioned media using microchannel chips. PANC-1 TSs and aPSCs were indirectly cocultured, whereas NK-92 cells were allowed to infiltrate the TS channel using convective medium flow. RESULTS: Coculture with aPSCs promoted PANC-1 TSs growth and suppressed the antitumor cytotoxic effects of NK-92 cells. Mutual inhibition of cellular activity without compromising migration ability was observed between aPSCs and NK-92 cells. Moreover, the reduced killing activity of NK-92 cells was found to be related with reduced granzyme B expression in NK cells. CONCLUSIONS: Herein, a novel TIME-on-chip model based on the coculture of PANC-1 TSs, aPSCs, and NK-92 cells was described. This model may be useful for studying the detailed mechanisms underlying NK cells dysregulation and for exploring future therapeutic interventions to restore NK cell activity in the tumor microenvironment.

Fatal outcome of severe fever with thrombocytopenia syndrome (SFTS) and severe and critical COVID-19 is associated with the hyperproduction of IL-10 and IL-6 and the low production of TGF-ß.

Severe fever with thrombocytopenia syndrome virus (SFTSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause the hyperproduction of inflammatory cytokines, which have pathological effects in patient including severe or fatal cytokine storms. To characterize the effect of SFTSV and SARS-CoV-2 infection on the production of cytokines in severe fever with thrombocytopenia syndrome (SFTS) and COVID-19 patients, we performed an analysis of cytokines in SFTS and COVID-19 patients and also investigated the role of interleukin-10 (IL-10) in vitro studies: lipopolysaccharide-induced THP-1-derived macrophages, SFTSV infection of THP-1 cells, and SARS-CoV-2 infection of THP-1 cells. In this study, we found that levels of both IL-10 and IL-6 were significantly elevated, the level of transforming growth factor-ß (TGF-ß) was significantly decreased and IL-10 was elevated earlier than IL-6 in severe and critical COVID-19 and fatal SFTS patients, and inhibition of IL-10 signaling decreased the production of IL-6 and elevated that of TGF-ß. Therefore, the hyperproduction of IL-10 and IL-6 and the low production of TGF-ß have been linked to cytokine storm-induced mortality in fatal SFTS and severe and critically ill COVID-19 patients and that IL-10 can play an important role in the host immune response to severe and critical SARS-CoV-2 and fatal SFTSV infection.

Deep learning-based detection algorithm for brain metastases on black blood imaging.

Brain metastases (BM) are the most common intracranial tumors, and their prevalence is increasing. High-resolution black-blood (BB) imaging was used to complement the conventional contrast-enhanced 3D gradient-echo imaging to detect BM. In this study, we propose an efficient deep learning algorithm (DLA) for BM detection in BB imaging with contrast enhancement scans, and assess the efficacy of an automatic detection algorithm for BM. A total of 113 BM participants with 585 metastases were included in the training cohort for five-fold cross-validation. The You Only Look Once (YOLO) V2 network was trained with 3D BB sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) images to investigate the BM detection. For the observer performance, two board-certified radiologists and two second-year radiology residents detected the BM and recorded the reading time. For the training cohort, the overall performance of the five-fold cross-validation was 87.95%, 24.82%, 19.35%, 14.48, and 18.40 for sensitivity, precision, F1-Score, the false positive average for the BM dataset, and the false positive average for the normal individual dataset, respectively. For the comparison of reading time with and without DLA, the average reading time was reduced by 20.86% in the range of 15.22-25.77%. The proposed method has the potential to detect BM with a high sensitivity and has a limited number of false positives using BB imaging.

Capmatinib in MET Exon 14 Skipping Mutation-Positive Lung Adenocarcinoma with Extensive Central Nervous System Metastasis.

Several selective mesenchymal-epithelial transition (MET) inhibitors have recently demonstrated favorable systemic efficacy in MET exon 14 skipping mutation-positive non-small cell lung cancer. However, there are limited data on their efficacy against central nervous system (CNS) metastasis, especially leptomeningeal seeding. Recently, we encountered a case of a 65-year-old woman who was diagnosed with metastatic lung adenocarcinoma. As routine molecular testing showed no genomic alterations, including epidermal growth factor receptor mutation and anaplastic lymphoma kinase translocation, the patient received a frontline platinum-doublet followed by paclitaxel. However, the tumor did not respond to these therapies, and her condition became deleterious owing to extensive brain and leptomeningeal metastases. Plasma genotyping revealed that the tumor harbored a MET exon 14 skipping mutation, and we started capmatinib, a selective MET inhibitor. The CNS lesions markedly decreased and the performance status of the patient dramatically improved. Our report highlights the significant CNS activity of capmatinib, even in cases of leptomeningeal metastasis. In addition, this report emphasizes the importance of the active utilization of molecular profiling to detect rare but druggable genetic alterations for the better management of patients with lung cancer.

Calcipotriol, a synthetic Vitamin D analog, promotes antitumor immunity via CD4+T-dependent CTL/NK cell activation.

To overcome the hurdles of immunotherapy, we investigated whether calcipotriol, a synthetic vitamin D analog, could overcome the immune evasion of glioblastoma multiforme (GBM) by modulating immune responses and the immunosuppressive tumor microenvironment. Administration of calcipotriol considerably reduced tumor growth. Both in vivo and in vitro studies revealed that CD8+T and natural killer (NK) cell gene signatures were enriched and activated, producing high levels of IFN-γ and granzyme B. In contrast, regulatory T cells (Treg) were significantly reduced in the calcipotriol-treated group. The expression of CD127, the receptor for thymic stromal lymphopoietin (TSLP), is elevated in CD4+T cells and potentially supports T-cell priming. Depleting CD4+T cells, but not NK or CD8+T cells, completely abrogated the antitumor efficacy of calcipotriol. These data highlight that the calcipotriol/TSLP/CD4+T axis can activate CD8+T and NK cells with a concomitant reduction in the number of Tregs in GBM. Therefore, calcipotriol can be a novel therapeutic modality to overcome the immune resistance of GBM by converting immunologically "cold" tumors into "hot" tumors. DATA AVAILABILITY: Data are available upon reasonable request. The RNA-seq dataset comparing the transcriptomes of control and calcipotriol-treated GL261 tumors is available from the corresponding author upon request.

Reliable quality assurance of X-ray mammography scanner by evaluation the standard mammography phantom image using an interpretable deep learning model.

OBJECTIVE: Mammography is the initial examination to detect breast cancer symptoms, and quality control of mammography devices is crucial to maintain accurate diagnosis and to safeguard against degradation of performance. The objective of this study was to assist radiologists in mammography phantom image evaluation by developing and validating an interpretable deep learning model capable of objectively evaluating the quality of standard phantom images for mammography. MATERIALS AND METHODS: A total of 2,208 mammography phantom images were collected for periodic accreditation of the scanner from 1,755 institutions. The dataset was randomly split into training (1,808 images) and testing (400 images) datasets with subgroups (76 images) for the multi-reader study. To develop an interpretable model that contains two deep learning networks in series, five processing steps were performed: mammography phantom detection, phantom object detection, post-processing, score evaluation, and a report with a comment about ambiguous results. RESULTS: For phantom detection, the accuracy and mean intersection over union (mIOU) were 1.00 and 0.938 in the test dataset, respectively. During phantom object detection, a total of 6,369 out of 6,400 objects were detected as the correct object class, and the accuracy and mIOU were 0.995 and 0.813, respectively. The predicted score for each object showed a consensus of 97.40% excluding ambiguous points and 59.10% for ambiguous points of the groups. CONCLUSIONS: The interpretable deep learning model using large-scale data from multiple centers shows high performance and reasonable object scoring, successfully validating the reliability and feasibility of mammography phantom image quality management.

Targeting TCTP sensitizes tumor to T cell-mediated therapy by reversing immune-refractory phenotypes.

Immunotherapy has emerged as a powerful approach to cancer treatment. However, immunotherapeutic resistance limits its clinical application. Therefore, identifying immune-resistant factors, which can be targeted by clinically available drugs and it also can be a companion diagnostic marker, is needed to develop combination strategies. Here, using the transcriptome data of patients, and immune-refractory tumor models, we identify TCTP as an immune-resistance factor that correlates with clinical outcome of anti-PD-L1 therapy and confers immune-refractory phenotypes, decreased T cell trafficking to the tumor and resistance to cytotoxic T lymphocyte-mediated tumor cell killing. Mechanistically, TCTP activates the EGFR-AKT-MCL-1/CXCL10 pathway by phosphorylation-dependent interaction with Na, K ATPase. Furthermore, treatment with dihydroartenimsinin, the most effective agent impending the TCTP-mediated-refractoriness, synergizes with T cell-mediated therapy to control immune-refractory tumors. Thus, our findings suggest a role of TCTP in promoting immune-refractoriness, thereby encouraging a rationale for combination therapies to enhance the efficacy of T cell-mediated therapy.

Diagnostic Challenge in Rapidly Growing Langerhans Cell Histiocytosis with Aneurysmal Bone Cyst in the Maxilla: A Case Report.

Langerhans cell histiocytosis (LCH) is a rare neoplastic disorder characterized by the clonal proliferation of CD1a +/CD 207 + dendritic cells, whose features are similar to those of epidermal Langerhans cells. LCH is more common in children than in adults. Localized osteolytic lesions in the craniofacial bones are the most common manifestations of LCH. However, LCH can also present as a multifocal and multisystem disease with poor prognosis. Locally aggressive LCH needs to be differentiated from various diseases such as osteomyelitis, malignant bone tumors, and soft tissue sarcomas. However, it is difficult to diagnose, since the imaging findings are nonspecific. We report a case of a highly aggressive LCH in the maxilla accompanied by a fluid-fluid level.

The Clinical Significance of the Hyperintense Acute Reperfusion Marker Sign in Subacute Infarction Patients.

PURPOSE: The hyperintense acute reperfusion marker (HARM) is characterized by the delayed enhancement of the subarachnoid or subpial space observed on postcontrast fluid-attenuated inversion recovery (FLAIR) images, and is considered a cerebral reperfusion marker for various brain disorders, including infarction. In this study, we evaluated the cerebral distribution patterns of HARM for discriminating between an enhancing subacute infarction and an enhancing mass located in the cortex and subcortical white matter. MATERIALS AND METHODS: We analyzed consecutive patients who experienced a subacute ischemic stroke, were hospitalized, and underwent conventional brain magnetic resonance imaging including postcontrast FLAIR within 14 days from symptom onset, as well as those who had lesions corresponding to a clinical sign detected by diffusion-weighted imaging and postcontrast T1-weighted imaging between May 2019 and May 2021. A total of 199 patients were included in the study. Of them, 94 were finally included in the subacute infarction group. During the same period, 76 enhancing masses located in the cortex or subcortical white matter, which were subcategorized as metastasis, malignant glioma, and lymphoma, were analyzed. We analyzed the overall incidence of HARM in subacute ischemic stroke cases, and compared the enhancement patterns between cortical infarctions and cortical masses. RESULTS: Among 94 patients with subacute stroke, 78 patients (83%) presented HARM, and among 76 patients with subcortical masses, 48 patients (63%) presented peripheral rim enhancement. Of 170 subcortical enhancing lesions, 88 (51.8%) showed HARM, and 78 (88.6%) were determined to be subacute infarction. Among 94 patients with subacute stroke, 48 patients (51%) had diffusion restrictions, and HARM was found in 39 patients (81.2%). Of the 46 patients (49%) without diffusion restriction, 39 patients (84.8%) showed HARM. CONCLUSIONS: The presence of HARM was significantly associated with subacute infarctions. For the masses, a peripheral rim enhancement pattern was observed around the mass rather than the cerebral sulci on postcontrast FLAIR.

IL-6 and IL-10 Levels, Rather Than Viral Load and Neutralizing Antibody Titers, Determine the Fate of Patients With Severe Fever With Thrombocytopenia Syndrome Virus Infection in South Korea.

Severe fever with thrombocytopenia syndrome (SFTS) is a new tick-borne viral disease, and most SFTS virus (SFTSV) infections occur via bites from the tick Haemaphysalis longicornis; however, SFTSV transmission can also occur through close contact with an infected patient. SFTS is characterized by acute high fever, thrombocytopenia, leukopenia, elevated serum hepatic enzyme levels, gastrointestinal symptoms, and multiorgan failure and has a 16.2 to 30% mortality rate. In this study, we found that age, dyspnea rates, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, multiorgan dysfunction score (MODS), viral load, IL-6 levels, and IL-10 levels were higher in patients with fatal disease than in patients with nonfatal disease during the initial clinical course of SFTS. In addition, we found that IL-6 and IL-10 levels, rather than viral load and neutralizing antibody titers, in patients with an SFTSV infection strongly correlated with outcomes (for severe disease with an ultimate outcome of recovery or death).

Novel Approaches to Detection of Cerebral Microbleeds: Single Deep Learning Model to Achieve a Balanced Performance.

PURPOSE: Cerebral microbleeds (CMBs) are considered essential indicators for the diagnosis of cerebrovascular disease and cognitive disorders. Traditionally, CMBs are manually interpreted based on criteria including the shape, diameter, and signal characteristics after an MR examination, such as susceptibility-weighted imaging or gradient echo imaging (GRE). In this paper, an efficient method for CMB detection in GRE scans is presented. MATERIALS AND METHODS: The proposed framework consists of the following phases: (1) pre-processing (skull extraction), (2) the first training with the ground truth labeled using CMB, (3) the second training with the ground truth labeled with CMB mimicking the same subjects, and (4) post-processing (cerebrospinal fluid (CSF) filtering). The proposed technique was validated on a dataset of 1133 CBMs that consisted of 5284 images for training and 1737 images for testing. We applied a two-stage approach using a region-based CNN method based on You Only Look Once (YOLO) to investigate a novel CMB detection technique. RESULTS: The sensitivity, precision, F1-score and false positive per person (FPavg) were evaluated as 80.96, 60.98, 69.57 and 6.57, 59.69, 62.70, 61.16 and 4.5, 66.90, 79.75, 72.76 and 2.15 for YOLO with a single label, YOLO with double labels, and YOLO + CSF filtering, respectively, and YOLO + CSF filtering showed the highest precision performance, F1-score and lowest FPavg. CONCLUSIONS: Using proposed framework, we developed an optimized CMB learning model with low false positives and a balanced performance in clinical practice.

Development and evaluation of a T1 standard brain template for Alzheimer disease.

BACKGROUND: Patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) have high variability in brain tissue loss, making it difficult to use a disease-specific standard brain template. The objective of this study was to develop an AD-specific three-dimensional (3D) T1 brain tissue template and to evaluate the characteristics of the populations used to form the template. METHODS: We obtained 3D T1-weighted images from 294 individuals, including 101 AD, 96 amnestic MCI, and 97 cognitively normal (CN) elderly individuals, and segmented them into different brain tissues to generate AD-specific brain tissue templates. Demographic data and clinical outcome scores were compared between the three groups. Voxel-based analyses and regions-of-interest-based analyses were performed to compare gray matter volume (GMV) and white matter volume (WMV) between the three participant groups and to evaluate the relationship of GMV and WMV loss with age, years of education, and Mini-Mental State Examination (MMSE) scores. RESULTS: We created high-resolution AD-specific tissue probability maps (TPMs). In the AD and MCI groups, losses of both GMV and WMV were found with respect to the CN group in the hippocampus (F >44.60, P<0.001). GMV was lower with increasing age in all individuals in the left (r=-0.621, P<0.001) and right (r=-0.632, P<0.001) hippocampi. In the left hippocampus, GMV was positively correlated with years of education in the CN groups (r=0.345, P<0.001) but not in the MCI (r=0.223, P=0.0293) or AD (r=-0.021, P=0.835) groups. WMV of the corpus callosum was not significantly correlated with years of education in any of the three subject groups (r=0.035 and P=0.549 for left, r=0.013 and P=0.821 for right). In all individuals, GMV of the hippocampus was significantly correlated with MMSE scores (left, r=0.710 and P<0.001; right, r=0.680 and P<0.001), while WMV of the corpus callosum showed a weak correlation (left, r=0.142 and P=0.015; right, r=0.123 and P=0.035). CONCLUSIONS: A 3D, T1 brain tissue template was created using imaging data from CN, MCI, and AD participants considering the participants' age, sex, and years of education. Our disease-specific template can help evaluate brains to promote early diagnosis of MCI individuals and aid treatment of MCI and AD individuals.