Intrahepatic cholangiocarcinoma detected on 18F-PSMA-1007 PET/MR imaging in a prostate cancer patient: a case report and literature review.

Radionuclide probes-targeted prostate-specific membrane antigen (PSMA) is used in diagnosis and treatment of prostate cancer (PCa). Recent studies have shown that PSMA is expressed in the tumor neovascular endothelium, such as in malignant liver tumors. We report a case of PCa with incidental intrahepatic cholangiocarcinoma (ICC) detection using 18F-PSMA-1007 and 18F-fluorodeoxyglucose (FDG) positron emission topography (PET)/MRI.18F-PSMA-1007 PET/MRI of our patient with PCa showed that one liver lesion had high PSMA uptake. 18F-FDG PET/MRI revealed minimal FDG uptake in the liver lesion. Histopathological examination revealed that the liver lesion was moderately to poorly differentiated cholangiocarcinoma. Our studies, along with others, demonstrated that malignant liver tumors, such as ICC, hepatocellular carcinoma (HCC), and combined hepatocellular-cholangiocarcinoma (CHC), and benign lesions, such as benign liver hemangioma, focal nodular hyperplasia, focal inflammation and steatosis, vascular malformation, and fatty sparing, exhibited elevated PSMA uptake. Moreover, PSMA-PET was superior to FDG-PET in detecting ICC and HCC, indicating that PSMA-PET may be used as alternative staging and to identify patients for PSMA-targeted therapy.

The Added Value of Contrast-Enhanced 68Ga-FAPI-04 PET/MRI Over 18F-FDG PET/CT in Hepatocellular Carcinoma.

ABSTRACT: A 43-year-old man with chronic hepatitis B and elevated alpha-fetoprotein levels showed no malignant evidence on 18F-FDG PET/CT. However, subsequent assessment using 68Ga-FAPI-04 PET/MR identified a lesion with increased FAPI uptake in the liver, coupled with detailed enhancement patterns on MRI, leading to a diagnosis of hepatocellular carcinoma, later confirmed by pathology. This case highlights the pivotal role of integrated 68Ga-FAPI-04 PET and enhanced MRI in refining hepatocellular carcinoma diagnostics, advancing a more nuanced imaging approach over conventional modalities for comprehensive evaluation of hepatic lesions.

Tau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer's disease.

The associations of synaptic loss with amyloid-ß (Aß) and tau pathology measured by positron emission tomography (PET) and plasma analysis in Alzheimer's disease (AD) patients are unknown. Seventy-five participants, including 26 AD patients, 19 mild cognitive impairment (MCI) patients, and 30 normal controls (NCs), underwent [18F]SynVesT-1 PET/MR scans to assess synaptic density and [18F]florbetapir and [18F]MK6240 PET/CT scans to evaluate Aß plaques and tau tangles. Among them, 19 AD patients, 12 MCI patients, and 29 NCs had plasma Aß42/40 and p-tau181 levels measured by the Simoa platform. Twenty-three individuals, 6 AD patients, 4 MCI patients, and 13 NCs, underwent [18F]SynVesT-1 PET/MRI and [18F]MK6240 PET/CT scans during a one-year follow-up assessment. The associations of Aß and tau pathology with cross-sectional and longitudinal synaptic loss were investigated using Pearson correlation analyses, generalized linear models and mediation analyses. AD patients exhibited lower synaptic density than NCs and MCI patients. In the whole cohort, global Aß deposition was associated with synaptic loss in the medial (r = -0.431, p < 0.001) and lateral (r = -0.406, p < 0.001) temporal lobes. Synaptic density in almost all regions was related to the corresponding regional tau tangles independent of global Aß deposition in the whole cohort and stratified groups. Synaptic density in the medial and lateral temporal lobes was correlated with plasma Aß42/40 (r = 0.300, p = 0.020/r = 0.289, p = 0.025) and plasma p-tau 181 (r = -0.412, p = 0.001/r = -0.529, p < 0.001) levels in the whole cohort. Mediation analyses revealed that tau tangles mediated the relationship between Aß plaques and synaptic density in the whole cohort. Baseline tau pathology was positively associated with longitudinal synaptic loss. This study suggested that tau burden is strongly linked to synaptic density independent of Aß plaques, and also can predict longitudinal synaptic loss.

APOE ε4 is associated with decreased synaptic density in cognitively impaired participants.

INTRODUCTION: We aimed to investigate the effect of apolipoprotein E4 (APOE) ε4 on synaptic density in cognitively impaired (CI) participants. METHODS: One hundred ten CI participants underwent amyloid positron emission tomography (PET) with 18F-florbetapir and synaptic density PET with 18F-SynVesT-1. We evaluated the influence of APOE ε4 allele on synaptic density and investigated the effects of ε4 genotype on the associations of synaptic density with Alzheimer's disease (AD) biomarkers. The mediation effects of AD biomarkers on ε4-associated synaptic density loss were analyzed. RESULTS: Compared with non-carriers, APOE ε4 allele carriers exhibited significant synaptic loss in the medial temporal lobe. Amyloid beta (Aß) and tau pathology mediated the effects of APOE ε4 on synaptic density to different extents. The associations between synaptic density and tau pathology were regulated by the APOE ε4 genotype. DISCUSSION: The APOE ε4 allele was associated with decreased synaptic density in CI individuals and may be driven by AD biomarkers.

Kinetic analysis of cardiac dynamic 18F-Florbetapir PET in healthy volunteers and amyloidosis patients: A pilot study.

Objectives: This study aimed to explore the potential of full dynamic PET kinetic analysis in assessing amyloid binding and perfusion in the cardiac region using 18F-Florbetapir PET, establishing a quantitative approach in the clinical assessment of cardiac amyloidosis disease. Materials & methods: The distribution volume ratios (DVRs) and the relative transport rate constant (R1), were estimated by a pseudo-simplified reference tissue model (pSRTM2) and pseudo-Logan plot (pLogan plot) with kidney reference for the region of interest-based and voxel-wise-based analyses. The parametric images generated using the pSRTM2 and linear regression with spatially constrained (LRSC) algorithm were then evaluated. Semi-quantitative analyses include standardized uptake value ratios at the early phase (SUVREP, 0.5-5 min) and late phase (SUVRLP, 50-60 min) were also calculated. Results: Ten participants [7 healthy controls (HC) and 3 cardiac amyloidosis (CA) subjects] underwent a 60-min dynamic 18F-Florbetapir PET scan. The DVRs estimated from pSRTM2 and Logan plot were significantly increased (HC vs CA; DVRpSRTM2: 0.95 ± 0.11 vs 2.77 ± 0.42, t'(2.13) = 7.39, P = 0.015; DVRLogan: 0.80 ± 0.12 vs 2.90 ± 0.55, t'(2.08) = 6.56, P = 0.020), and R1 were remarkably decreased in CA groups, as compared to HCs (HC vs CA; 1.08 ± 0.37 vs 0.56 ± 0.10, t'(7.63) = 3.38, P = 0.010). The SUVREP and SUVRLP were highly correlated to R1 (r = 0.97, P < 0.001) and DVR(r = 0.99, P < 0.001), respectively. The DVRs in the total myocardium region increased slightly as the size of FWHM increased and became stable at a Gaussian filter ≥6 mm. The secular equilibrium of SUVR was reached at around 50-min p.i. time. Conclusion: The DVR and R1 estimated from cardiac dynamic 18F-Florbetapir PET using pSRTM with kidney pseudo-reference tissue are suggested to quantify cardiac amyloid deposition and relative perfusion, respectively, in amyloidosis patients and healthy controls. We recommend a dual-phase scan: 0.5-5 min and 50-60 min p.i. as the appropriate time window for clinically assessing cardiac amyloidosis and perfusion measurements using 18F-Florbetapir PET.

Metabotropic glutamate receptor 5 (mGluR5) is associated with neurodegeneration and amyloid deposition in Alzheimer's disease: A [18F]PSS232 PET/MRI study.

BACKGROUND: Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the initial pathophysiological mechanism of Alzheimer's disease (AD). The study aims to investigate the association between mGluR5 availability and AD's biomarkers and cognitive function. METHODS: We examined 35 individuals with mGluR5 tracer [18F]PSS232 to assess mGluR5 availability, and with [18F]Florbetapir PET to assess global amyloid deposition, and [18F]FDG PET to assess glucose metabolism. The plasma neurofilament light (NfL) and p-tau181 levels in a subset of individuals were measured (n = 27). The difference in mGluR5 availability between the AD and normal control (NC) groups was explored. The associations of mGluR5 availability with amyloid deposition, glucose metabolism, gray matter volume (GMV), neuropsychological assessment scores, and plasma biomarkers were analyzed. RESULTS: The mGluR5 availability was significantly reduced in AD patients' hippocampus and parahippocampal gyrus compared to NCs. Global amyloid deposition was positively associated with mGluR5 availability in the AD group and reversely associated in the NC group. The mGluR5 availability was positively correlated with regional glucose metabolism in the overall and stratified analyses. The availability of mGluR5 in the hippocampus and parahippocampal gyrus demonstrated a strong relationship with the GMV of the medial temporal lobe, plasma p-tau181 or NfL levels, and global cognitive performance. CONCLUSIONS: [18F]PSS232 PET can quantify the changes of mGluR5 availability in the progression of AD. mGluR5 availability correlated not only with neuropathological biomarkers of AD but also with neurodegenerative biomarkers and cognitive performance. mGluR5 may be a novel neurodegenerative biomarker, and whether mGluR5 could be a potential therapeutic target for AD needs to be further studied.

Diagnostic capability of 18F-PSMA PET-MRI and pelvic MRI plus bone scan in treatment-naive prostate cancer: a single-center paired validating confirmatory study.

BACKGROUND: Radical prostatectomy with pelvic lymph node dissection for the treatment of high-risk localized prostate cancer (PCa) results in long-term benefits in selected patients. But insufficient sensitivity of conventional examinations which are pelvic MRI and bone scan, limits the diagnosis of bone and lymph node metastasis of PCa. This affects the surgical management strategy of a large number of patients. The purpose of this study was to investigate whether 18F-prostate-specific membrane antigen (PSMA) PET-MRI could improve the clinical detection of PCa metastases compared with the conventional pelvic MRI plus bone scan. MATERIALS AND METHODS: From April 2020 to April 2023, we prospectively enroled 472 patients with histologically proven PCa in our centre, and 120 patients underwent 18F-PSMA PET-MRI, multiparametric MRI, and bone scan before laparoscopic radical prostatectomy plus lymph node dissection. The accuracy of imaging results in detecting lymph node and bone metastatic lesions was compared between PSMA PET-MRI and MRI plus bone scan. RESULTS: In diagnosing lymph node metastasis, PSMA PET-MRI had an area under the curve (AUC) of 0.844 (95% CI: 0.738-0.949, P < 0.001), sensitivity and specificity of 75% and 96%, which performed apparently better than MRI [AUC=0.615 (95% CI: 0.480-0.750, P =0.073)]. PSMA PET-MRI showed excellent expression in the diagnosis of bone metastases, with an AUC of 0.910 (95% CI: 0.840-0.981, P <0.001) compared to 0.700 (95% CI: 0.577-0.823, P =0.001) in bone scanning. PSMA PET-MRI also had higher sensitivity than bone scanning (90% vs. 43%), while lower specificity (92% vs. 97%). CONCLUSION: PSMA PET-MRI is superior to conventional imaging at diagnosing metastases in lymph nodes and bones in PCa and can provide a more accurate stagement.

Generation of Human Blood Vessel and Vascularized Cerebral Organoids.

Brain organoids have been widely used to study diseases and the development of the nervous system. Many reports have investigated the application of brain organoids, but most of these models lack vascular structures, which play essential roles in brain development and neurological diseases. The brain and blood vessels originate from two different germ layers, making it difficult to induce vascularized brain organoids in vitro. We developed this protocol to generate brain-specific blood vessel and cerebral organoids and then fused them at a specific developmental time point. The fused cerebral organoids exhibited robust vascular network-like structures, which allows simulating the in vivo developmental processes of the brain for further applications in various neurological diseases. Key Features • Culturing vascularized brain organoids using human embryonic stem cells (hESCs). • The new approach generates not only neural cells and vessel-like networks but also brain-resident microglia immune cells in a single organoid.

Comprehensive spatiotemporal mapping of single-cell lineages in developing mouse brain by CRISPR-based barcoding.

A fundamental interest in developmental neuroscience lies in the ability to map the complete single-cell lineages within the brain. To this end, we developed a CRISPR editing-based lineage-specific tracing (CREST) method for clonal tracing in Cre mice. We then used two complementary strategies based on CREST to map single-cell lineages in developing mouse ventral midbrain (vMB). By applying snapshotting CREST (snapCREST), we constructed a spatiotemporal lineage landscape of developing vMB and identified six progenitor archetypes that could represent the principal clonal fates of individual vMB progenitors and three distinct clonal lineages in the floor plate that specified glutamatergic, dopaminergic or both neurons. We further created pandaCREST (progenitor and derivative associating CREST) to associate the transcriptomes of progenitor cells in vivo with their differentiation potentials. We identified multiple origins of dopaminergic neurons and demonstrated that a transcriptome-defined progenitor type comprises heterogeneous progenitors, each with distinct clonal fates and molecular signatures. Therefore, the CREST method and strategies allow comprehensive single-cell lineage analysis that could offer new insights into the molecular programs underlying neural specification.

Mapping of clonal lineages across developmental stages in human neural differentiation.

The cell lineages across developmental stages remain to be elucidated. Here, we developed single-cell split barcoding (SISBAR) that allows clonal tracking of single-cell transcriptomes across stages in an in vitro model of human ventral midbrain-hindbrain differentiation. We developed "potential-spective" and "origin-spective" analyses to investigate the cross-stage lineage relationships and mapped a multi-level clonal lineage landscape depicting the whole differentiation process. We uncovered many previously uncharacterized converging and diverging trajectories. Furthermore, we demonstrate that a transcriptome-defined cell type can arise from distinct lineages that leave molecular imprints on their progenies, and the multilineage fates of a progenitor cell-type represent the collective results of distinct rather than similar clonal fates of individual progenitors, each with distinct molecular signatures. Specifically, we uncovered a ventral midbrain progenitor cluster as the common clonal origin of midbrain dopaminergic (mDA) neurons, midbrain glutamatergic neurons, and vascular and leptomeningeal cells and identified a surface marker that can improve graft outcomes.

In vivo synaptic density loss correlates with impaired functional and related structural connectivity in Alzheimer's disease.

Synapse loss has been considered as a major pathological change in Alzheimer's disease (AD). It remains unclear about whether and how synapse loss relates to functional and structural connectivity dysfunction in AD. We measured synaptic vesicle glycoprotein 2 A (SV2A) binding using 18F-SynVesT-1 PET to evaluate synaptic alterations in 33 participants with AD, 31 with mild cognitive impairment (MCI), and 30 controls. We examined the correlation between synaptic density and cognitive function. Functional MRI was performed to analyze functional connectivity in lower synaptic density regions. We tracked the white matter tracts between impaired functional connectivity regions using Diffusion MRI. In AD group, lower synaptic density in bilateral cortex and hippocampus was found when compared with controls. The synaptic density changes in right insular cortex and bilateral caudal middle frontal gyrus (MFG) were correlated with cognitive decline. Among them, right MFG synaptic density was positively associated with right MFG - bilateral superior frontal gyrus (SFG) functional connectivity. AD had lower probability of tract (POT) between right MFG and SFG than controls, which was significantly associated with global cognition. These findings provide evidence supporting synapse loss contributes to functional and related structural connectivity alterations underlying cognitive impairment of AD.

Non-tumoral uptake of 68Ga-FAPI-04 PET: A retrospective study.

Objective: Fibroblast activation protein (FAP)-targeting radiopharmaceutical based on the FAP-specific inhibitor (FAPI) is considered as a potential alternative agent to FDG for tumor-specific imaging. However, FAP is also expressed in normal adult tissues. The aim of this study was to explore the image features of non-tumoral regions with high uptake of 68Ga-FAPI-04 in positron emission tomography (PET) imaging and to reveal the physiological mechanisms of these regions. Material: A total of 137 patients who underwent whole-body 68Ga-FAPI-04 PET/MR (n=46) or PET/CT (n=91) were included in this retrospective study. Three experienced nuclear medicine physicians determined the non-tumoral regions according to other imaging modalities (CT, MRI, 18F-FDG PET, or ultrasound), clinical information, or pathological results. The regions of interest (ROIs) were drawn manually, and the maximum standardized uptake value (SUVmax) was measured. Results: A total of 392 non-tumoral uptake regions were included in this study. The included physiological regions were uterus (n=38), submandibular gland (n=118), nipple (n=37), gingiva (n=65), and esophagus (n=31). The incidence of 68Ga-FAPI-04 uptake in physiological regions was independent of age, the tracer uptakes in the gingiva and esophagus were more common in male patients (p=0.006, 0.009), while that in the nipple was more common in female patients (p < 0.001). The included benign regions were inflammatory lymph node (n =10), pneumonia (n=13), atherosclerosis (n=10), pancreatitis (n=18), osteosclerosis (n=45), and surgical scar (n=7). No significant difference was observed in SUVmax between physiological and benign regions. Conclusions: A number of organs exhibit physiological uptakes of 68Ga-FAPI-04. Our study showed that regions with high 68Ga-FAPI-04 uptake did not necessarily represent malignancy. Being familiar with physiological and typical benign 68Ga-FAPI-04 uptake regions can be helpful for physicians to interpret images and to make an accurate diagnosis.

Fast generation of forebrain oligodendrocyte spheroids from human embryonic stem cells by transcription factors.

Oligodendrocyte spheroids (OL-spheroids) containing oligodendrocytes and neurons provide an accessible system to dissect demyelinating diseases and test therapeutic treatment. However, generation of human OL-spheroids is still technically challenging and time-consuming until now. Here, we presented evidence that overexpression of SOX10 and OLIG2 (SO) in human embryonic stem cells (hESCs)-derived ventral forebrain neural progenitors is sufficient to produce forebrain pre-oligodendrocytes (pre-OLs) and mature oligodendrocytes (OLs) within 20-40 days. More importantly, optimizing this procedure by overexpression of SO in ventral forebrain spheroids, we successfully generated OL-spheroids with pre-OLs, mature OLs, and neurons 40 days after OL-induction. We further demonstrated oligodendrocyte-neuron interactions and obvious axon myelination in OL-spheroids. Finally, over 30% cells developed into mature oligodendrocytes with forebrain identity and myelinate axons in mouse brain 3 months after transplantation. This study provides a strategy to generate forebrain OL-spheroids rapidly and efficiently which would facilitate development of new therapeutics for demyelinating disorders.

Human midbrain dopaminergic neuronal differentiation markers predict cell therapy outcomes in a Parkinson's disease model.

Human pluripotent stem cell-based (hPSC-based) replacement therapy holds great promise for the treatment of Parkinson's disease (PD). However, the heterogeneity of hPSC-derived donor cells and the low yield of midbrain dopaminergic (mDA) neurons after transplantation hinder its broad clinical application. Here, we have characterized the single-cell molecular landscape during mDA neuron differentiation. We found that this process recapitulated the development of multiple but adjacent fetal brain regions including the ventral midbrain, the isthmus, and the ventral hindbrain, resulting in a heterogenous donor cell population. We reconstructed the differentiation trajectory of the mDA lineage and identified calsyntenin 2 (CLSTN2) and protein tyrosine phosphatase receptor type O (PTPRO) as specific surface markers of mDA progenitors, which were predictive of mDA neuron differentiation and could facilitate high enrichment of mDA neurons (up to 80%) following progenitor cell sorting and transplantation. Marker-sorted progenitors exhibited higher therapeutic potency in correcting motor deficits of PD mice. Different marker-sorted grafts had a strikingly consistent cellular composition, in which mDA neurons were enriched, while off-target neuron types were mostly depleted, suggesting stable graft outcomes. Our study provides a better understanding of cellular heterogeneity during mDA neuron differentiation and establishes a strategy to generate highly purified donor cells to achieve stable and predictable therapeutic outcomes, raising the prospect of hPSC-based PD cell replacement therapies.

A two-stage cardiac PET and late gadolinium enhancement MRI co-registration method for improved assessment of non-ischemic cardiomyopathies using integrated PET/MR.

PURPOSE: Respiratory motion causes mismatches between PET images of the myocardium and the corresponding cardiac MR images in cardiac integrated PET/MR. The mismatch may affect the attenuation correction and the diagnosis of non-ischemic cardiomyopathies. In this study, we present a two-stage cardiac PET and MR late gadolinium enhancement (LGE) co-registration method, which seeks to improve diagnostic accuracy of non-ischemic cardiomyopathies via better image co-registration using an integrated whole-body PET/MR system. METHODS: The proposed PET and LGE two-stage co-registration method was evaluated through comparison with one-stage direct co-registration and no-registration. One hundred and ninety-one slices of LGE and forty lesions were studied. Two trained nuclear medicine physicians independently assessed the displacement between LGE and PET to qualitatively evaluate the co-registration quality. The changes of the mean SUV in the normal myocardium and the LGE-enhanced lesions before and after image co-registration were measured to quantitatively evaluate the accuracy and value of image co-registration. RESULTS: The two-stage method had an improved image registration score (4.93 ± 0.89) compared with the no-registration method (3.49 ± 0.84, p value < 0.001) and the single-stage method (4.23 ± 0.81, p value < 0.001). Furthermore, the two-stage method led to increased SUV value in the myocardium (3.87 ± 2.56) compared with the no-registration method (3.14 ± 1.92, p value < 0.001) and the single-stage method (3.32 ± 2.16, p value < 0.001). The mean SUV in the LGE lesion significantly increased from 2.51 ± 2.09 to 2.85 ± 2.35 (p value < 0.001) after the two-stage co-registration. CONCLUSION: The proposed two-stage registration method significantly improved the co-registration between PET and LGE in integrated PET/MR imaging. The technique may improve diagnostic accuracy of non-ischemic cardiomyopathies via better image co-registration. REGISTERED NO: DF-2020-085,2020.04.30.

Comparison of [68 Ga]Ga-FAPI-04 and [18F]-FDG for the detection of primary and metastatic lesions in patients with gastric cancer: a bicentric retrospective study.

INTRODUCTION: The low sensitivity of [18F]-fluorodeoxyglucose ([18F]-FDG) for the diagnosis of gastric cancer limits its application. In this study, we aimed to investigate the potential advantage of [68 Ga]Ga-FAPI-04 over [18F]-FDG in the evaluation of gastric cancer. METHODS: This was a bicentric retrospective analysis of a prospective parent study (clinical trial: HS-KY-2020-826 (Huashan Hospital) and DF-2020-102 (Shanghai East Hospital)). Thirty-eight patients with gastric cancer (31 with adenocarcinoma and 7 with signet ring cell carcinoma) were included in this study. All of the participants underwent [68 Ga]Ga-FAPI-04 and [18F]-FDG imaging by positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance (MR). The scans were interpreted by two experienced nuclear medicine physicians, and the maximum standardized uptake value (SUVmax) was calculated. Histopathological findings obtained from biopsy or resected surgical specimens were used as a reference for the final diagnosis. RESULTS: For the detection of primary gastric cancer, the sensitivities of [68 Ga]Ga-FAPI-04 PET and [18F]-FDG PET were 100% (38/38) and 82% (31/38), respectively (P = 0.016). Four cases of adenocarcinoma and three cases of signet ring cell carcinoma were missed by [18F]-FDG PET. The mean SUVmax of [68 Ga]Ga-FAPI-04 in tumours greater than 4 cm (11.0 ± 4.5) was higher than that in tumours less than 4 cm (4.5 ± 3.2) (P = 0.0015). The mean SUVmax of [68 Ga]Ga-FAPI-04 was higher in T2-4 tumours (9.7 ± 4.4) than in T1 tumours (3.1 ± 1.5) (P = 0.0002). For the detection of metastatic lesions, the sensitivities of [68 Ga]Ga-FAPI-04 PET and [18F]-FDG PET in 10 patients with regional lymph node metastasis and distant metastasis were 6/10 and 5/10, respectively. CONCLUSION: In this selected cohort, [68 Ga]Ga-FAPI-04 PET had a superior detection rate than [18F]-FDG PET for primary gastric cancer. [68 Ga]Ga-FAPI-04 PET could provide better performance with regard to gastric cancer diagnosis and staging. Prospective clinical trials are warranted.

Evaluation of SUVlean consistency in FDG and PSMA PET/MR with Dixon-, James-, and Janma-based lean body mass correction.

PURPOSE: To systematically evaluate the consistency of various standardized uptake value (SUV) lean body mass (LBM) normalization methods in a clinical positron emission tomography/magnetic resonance imaging (PET/MR) setting. METHODS: SUV of brain, liver, prostate, parotid, blood, and muscle were measured in 90 18F-FDG and 28 18F-PSMA PET/MR scans and corrected for LBM using the James, Janma (short for Janmahasatian), and Dixon approaches. The prospective study was performed from December 2018 to August 2020 at Shanghai East Hospital. Forty dual energy X-ray absorptiometry (DXA) measurements of non-fat mass were used as the reference standard. Agreement between different LBM methods was assessed by linear regression and Bland-Altman statistics. SUV's dependency on BMI was evaluated by means of linear regression and Pearson correlation. RESULTS: Compared to DXA, the Dixon approach presented the least bias in LBM/weight% than James and Janma models (bias 0.4±7.3%, - 8.0±9.4%, and - 3.3±8.3% respectively). SUV normalized by body weight (SUVbw) was positively correlated with body mass index (BMI) for both FDG (e.g., liver: r = 0.45, p < 0.001) and PSMA scans (r = 0.20, p = 0.31), while SUV normalized by lean body mass (SUVlean) revealed a decreased dependency on BMI (r = 0.22, 0.08, 0.14, p = 0.04, 0.46, 0.18 for Dixon, James, and Janma models, respectively). The liver SUVbw of obese/overweight patients was significantly larger (p < 0.001) than that of normal patients, whereas the bias was mostly eliminated in SUVlean. One-way ANOVA showed significant difference (p < 0.001) between SUVlean in major organs measured using Dixon method vs James and Janma models. CONCLUSION: Significant systematic variation was found using different approaches to calculate SUVlean. A consistent correction method should be applied for serial PET/MR scans. The Dixon method provides the most accurate measure of LBM, yielding the least bias of all approaches when compared to DXA.

Standardized uptake values of 99mTc-MDP in normal vertebrae assessed using quantitative SPECT/CT for differentiation diagnosis of benign and malignant bone lesions.

BACKGROUND: Quantitative bone SPECT/CT is useful for disease follow up and inter-patient comparison. For bone metastatic malignant lesions, spine is the most commonly invaded site. However, Quantitative studies with large sample size investigating all the segments of normal cervical, thoracic and lumbar vertebrae are seldom reported. This study was to evaluate the quantitative tomography of normal vertebrae using 99mTc-MDP with SPECT/CT to investigate the feasibility of standardized uptake value (SUV) for differential diagnosis of benign and malignant bone lesions. METHODS: A retrospective study was carried out involving 221 patients (116 males and 105 females) who underwent SPECT/CT scan using 99mTc-MDP. The maximum SUV (SUVmax), mean SUV (SUVmean) and CT values (Hounsfield Unit, HU) of 2416 normal vertebrae bodies, 157 benign bone lesions and 118 malignant bone metastasis foci were obtained. The correlations between SUVmax of normal vertebrae and CT values of normal vertebrae, age, height, weight, BMI of patients were analyzed. Statistical analysis was performed with data of normal, benign and malignant groups corresponding to same sites and gender. RESULTS: The SUVmax and SUVmean of normal vertebrae in males were markedly higher than those in females (P < 0.0009). The SUVmax of each normal vertebral segment showed a strong negative correlation with CT values in both males and females (r = - 0.89 and - 0.92, respectively; P < 0.0009). The SUVmax of normal vertebrae also showed significant correlation with weight, height, and BMI in males (r = 0.4, P < 0.0009; r = 0.28, P = 0.005; r = 0.22, P = 0.026), and significant correlation with weight and BMI in females (r = 0.32, P = 0.009; r = 0.23, P = 0.031). The SUVmax of normal group, benign bone lesion group and malignant bone metastasis foci group showed statistical differences in both males and females. CONCLUSION: Our study evaluated SUVmax and SUVmean of normal vertebrae, benign bone lesion and malignant bone metastasis foci with a large sample population. Preliminary results proved the potential value of SUVmax in differentiation benign and malignant bone lesions. The results may provide a quantitative reference for clinical diagnosis and the evaluation of therapeutic response in vertebral lesions.

Human Stem Cell-Derived Neurons Repair Circuits and Restore Neural Function.

Although cell transplantation can rescue motor defects in Parkinson's disease (PD) models, whether and how grafts functionally repair damaged neural circuitry in the adult brain is not known. We transplanted hESC-derived midbrain dopamine (mDA) or cortical glutamate neurons into the substantia nigra or striatum of a mouse PD model and found extensive graft integration with host circuitry. Axonal pathfinding toward the dorsal striatum was determined by the identity of the grafted neurons, and anatomical presynaptic inputs were largely dependent on graft location, whereas inhibitory versus excitatory input was dictated by the identity of grafted neurons. hESC-derived mDA neurons display A9 characteristics and restore functionality of the reconstructed nigrostriatal circuit to mediate improvements in motor function. These results indicate similarity in cell-type-specific pre- and post-synaptic integration between transplant-reconstructed circuit and endogenous neural networks, highlighting the capacity of hPSC-derived neuron subtypes for specific circuit repair and functional restoration in the adult brain.