Unraveling olfactory subtypes in Parkinson's disease and their effect on the natural history of the disease.

BACKGROUND: Hyposmia in Parkinson's disease (PD) had been studied before but had not been detailed by its temporal progression. This study observed how each olfactory subtype evolved in terms of motor symptoms, cardiac sympathetic innervation, and cognition. METHODS: Two hundred and three early PD patients were classified as normosmia, hyposmia-converter (hypo-converter), and hyposmia. Their presynaptic monoamine availability at the time of diagnosis was assessed by positron emission tomography imaging using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and compared across the subtypes. Motor symptoms were evaluated in all patients, cardiac denervation was examined in 183 patients, and cognition in 195 patients were assessed using a neuropsychological battery. The domains were re-assessed 2-4 times, and the longitudinal data were analyzed to discern the natural course of each subtype. RESULTS: Twenty-nine (14.3%) patients belonged to the normosmia group, 34 (16.7%) to the hypo-converter group, and the rest to the hyposmia (69.0%) group. 85.7% of the total population became hyposmic during an average 3 years of follow-up. The baseline motor symptoms, cardiac denervation, and cognition were comparable across the olfactory subtypes. Across the subtypes, a decline in the presynaptic monoamine densities of the caudate, especially the ventral-anterior subdivisions, correlated inversely with olfaction dysfunction. Over time, motor and cardiac denervation burdens worsened regardless of olfactory subtypes, but hypo-converters experienced faster cognitive deterioration than the other two groups. CONCLUSIONS: The results suggest that the olfactory subtypes have differential significance along the disease course, which might reflect the involvement of different neuro-biochemical circuitries.

A Comparative Analysis of Two Automated Quantification Methods for Regional Cerebral Amyloid Retention: PET-Only and PET-and-MRI-Based Methods.

Accurate quantification of amyloid positron emission tomography (PET) is essential for early detection of and intervention in Alzheimer's disease (AD) but there is still a lack of studies comparing the performance of various automated methods. This study compared the PET-only method and PET-and-MRI-based method with a pre-trained deep learning segmentation model. A large sample of 1180 participants in the Catholic Aging Brain Imaging (CABI) database was analyzed to calculate the regional standardized uptake value ratio (SUVR) using both methods. The logistic regression models were employed to assess the discriminability of amyloid-positive and negative groups through 10-fold cross-validation and area under the receiver operating characteristics (AUROC) metrics. The two methods showed a high correlation in calculating SUVRs but the PET-MRI method, incorporating MRI data for anatomical accuracy, demonstrated superior performance in predicting amyloid-positivity. The parietal, frontal, and cingulate importantly contributed to the prediction. The PET-MRI method with a pre-trained deep learning model approach provides an efficient and precise method for earlier diagnosis and intervention in the AD continuum.

Dosimetric Analysis of a Phase I Study of PSMA-Targeting Radiopharmaceutical Therapy With [177Lu]Ludotadipep in Patients With Metastatic Castration-Resistant Prostate Cancer.

OBJECTIVE: 177Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [177Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [177Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [177Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organ- and tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. RESULTS: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. CONCLUSION: [177Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

Estimating motor progression trajectory pursuant to temporal dynamic status of cardiac denervation in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a multifaceted disease that encompasses diverse clinical phenotypes. The diversity of PD could be subtyped based on the temporal dynamic status of cardiac sympathetic innervation; (1) initially, denervated myocardium (peripheral nervous system-predominant; PNS-predominant), (2) preserved myocardium (central nervous system-predominant; CNS-predominant), and (3) preserved myocardium who developed cardiac sympathetic denervation (CSD) on the subsequent imaging (Converter; delayed cardiac denervation). This study assessed how the cardiac denervation could reflect the pathobiology. We investigated whether this phenotyping could help predict the motor progression trajectory of PD. METHODS: Cardiac sympathetic innervation was evaluated using initial and sequential 123I-meta-iodobenzylguanidine myocardial scintigraphy and patients were stratified into three groups as above. Motor severity and progression were evaluated in each patient. The association between subtypes and dopaminergic nigrostriatal degeneration was analyzed. The influence of cardiac denervation on motor progression was also investigated. RESULTS: Among the enrolled 195 patients, 144 PD subjects were defined as PNS-predominant, 16 as Converter, and 35 as CNS-predominant. The most severe nigrostriatal degeneration was observed in the PNS-predominant group and the dopaminergic degeneration was the most asymmetric in the CNS-predominant group. Positive linear trends of nigrostriatal degeneration and its asymmetric degeneration of striatum and globus pallidus were found across the patterns of cardiac sympathetic innervation (PNS-predominant vs. Converter vs. CNS-predominant). It indicated an increasing degree of asymmetric degeneration among the groups. A longitudinal estimation of motor progression revealed distinct cardiac denervation trajectories for each subtype. CONCLUSIONS: These results implicated that the subtypes of CSD might indicate a predominant origin and spreading pattern of pathobiology.

Cardiac sympathetic "morbidity" might reflect the neurobiology of early Parkinson's disease.

BACKGROUND: An appropriate extracranial biomarker that delineates endophenotypes of Parkinson's disease (PD) at an early stage and reflects the neurodegenerative process is lacking. An evaluation of myocardial sympathetic nerve terminals could be a good candidate. This study aimed to explore subtypes of PD patients that showed cardiac catecholaminergic vesicular defect and their characteristics. METHODS: This study included 122 early drug-naïve PD patients who were followed for approximately 4-5 years. All patients were examined with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane positron-emission tomography and 123I-meta-iodobenzylguanidine myocardial scintigraphy. Cardiac scans were reexamined two or three times. Patients were subgrouped into the sympathetic denervated group at the initial scan, those without evidence of denervated myocardium in the first and subsequent scans, and the converters whose myocardium was initially normal but became impaired in the subsequent scans. Cognition in 99 patients was initially assessed with neuropsychological tests. Any associations between cardiac denervation subtypes and presynaptic dopamine transporter densities were investigated. Cognitive status relevant to cardiac sympathetic denervation status was evaluated. RESULTS: This study found that cross-sectional comparisons of presynaptic monoamine transporter availability with a predefined order of cardiac denervation groups revealed parallel degeneration. A quadratic correlation between cardiac catecholamine capacity and cognition was observed. This association was interpreted to reflect the early neurobiology of PD. CONCLUSION: An observed cardiac catecholaminergic gradient was to mirror the central neurobiology of early PD.

SPECT/CT Radiomics for Differentiating between Enchondroma and Grade I Chondrosarcoma.

This study was performed to assess the value of SPECT/CT radiomics parameters in differentiating enchondroma and atypical cartilaginous tumors (ACTs) located in the long bones. Quantitative HDP SPECT/CT data of 49 patients with enchondromas or ACTs in the long bones were retrospectively reviewed. Patients were randomly split into training (n = 32) and test (n = 17) data, and SPECT/CT radiomics parameters were extracted. In training data, LASSO was employed for feature reduction. Selected parameters were compared with classic quantitative parameters for the prediction of diagnosis. Significant parameters from training data were again tested in the test data. A total of 12 (37.5%) and 6 (35.2%) patients were diagnosed as ACTs in training and test data, respectively. LASSO regression selected two radiomics features, zone-length non-uniformity for zone (ZLNUGLZLM) and coarseness for neighborhood grey-level difference (CoarsenessNGLDM). Multivariate analysis revealed higher ZLNUGLZLM as the only significant independent factor for the prediction of ACTs, with sensitivity and specificity of 85.0% and 58.3%, respectively, with a cut-off value of 191.26. In test data, higher ZLNUGLZLM was again associated with the diagnosis of ACTs, with sensitivity and specificity of 83.3% and 90.9%, respectively. HDP SPECT/CT radiomics may provide added value for differentiating between enchondromas and ACTs.

Exploring the link between essential tremor and Parkinson's disease.

Epidemiological studies have reported a link between essential tremor (ET) and Parkinson's disease (PD). Recent studies have suggested ET as a possible neurodegenerative disease whose subgroup contained Lewy bodies in the brainstem, as in PD. PD with antedated ET (PDconv) might exhibit traits different from those of the pure form of ET or PD. This study aimed to unveil the interplay between PD and premorbid ET, which might be the core pathobiology that differentiates PDconv from PD. The study included 51 ET, 32 PDconv, and 95 PD patients who underwent positron emission tomography using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and 123I-meta-iodobenzylguanidine myocardial scintigraphy to analyze central dopaminergic and peripheral noradrenergic integrity. The results show that PDconv group followed the typical striatal pathology of PD but with a delay in noradrenergic impairment as it caught up with the denervating status of PD a few years after PD diagnosis. Whereas the two PD subtypes displayed similar patterns of presynaptic dopamine transporter deficits, ET patients maintained high densities in all subregions except thalamus. Presynaptic dopaminergic availability decreased in a linear or quadratic fashion across the three groups (ET vs. PDconv vs. PD). The age at onset and duration of ET did not differ between pure ET and PDconv patients and did not influence the striatal monoamine status. The myocardium in PDconv patients was initially less denervated than in PD patients, but it degenerated more rapidly. These findings suggest that PDconv could be a distinctive subclass in which the pathobiology of PD interacts with that of ET in the early phase of the disease.

A 3-year natural history of orthostatic blood pressure dysregulation in early Parkinson's disease.

In Parkinson's disease (PD), cardiovascular dysautonomia accumulates with disease progression, but studies are lacking on the natural history behind each subtype except orthostatic hypotension. This study investigated the early natural history of orthostatic blood pressure (BP) subtypes in PD. Two hundred sixty-seven early PD patients were included. Their cardiovascular functions were assessed by head-up tilt-test and 123I-metaiodobenzylguanidine scintigraphy. All patients were classified as having supine hypertension (SH), orthostatic hypertension (OHT), delayed orthostatic hypotension (dOH), or orthostatic hypotension (OH) according to consensus criteria. The patients were assigned to one of three groups: extreme BP dysregulation (BPextreme), mild BP dysregulation (BPmild), and no BP dysregulation (BPnone) according to their orthostatic BP subtypes. The autonomic functions of 237 patients were re-assessed after approximately 3 years. Among initially enrolled subjects, 61.8% of the patients showed orthostatic BP dysregulation: 29.6% in the BPextreme group and 32.2% in the BPmild group. At follow-up, the BPextreme group increased in number, while the BPmild group diminished. Two-thirds of the initial BPextreme patients maintained their initial subtype at follow-up. In comparison, 40.7% of the initial BPmild patients progressed to the BPextreme group, and 32.4% and 14.7% of the initial BPnone group progressed to BPextreme and BPmild groups, respectively. Cardiac denervation was most severe in the BPextreme group, and a linear gradient of impairment was observed across the subtypes. In conclusion, various forms of positional BP dysregulation were observed during the early disease stage. SH and OH increased with disease progression, while OHT and dOH decreased, converting primarily to SH and/or OH.

Irreversible electroporation for prostate cancer using PSMA PET-CT.

Background: To demonstrate the clinical usefulness of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computerized tomography (CT) for irreversible electroporation (IRE) in prostate cancer patients. Methods: From January to May 2021, 17 men were diagnosed with localized prostate cancer through preoperative mpMRI and [18F] florastamin PSMA PET-CT imaging, followed by transperineal MRI-ultrasound fusion-guided biopsy. The patients underwent IRE focal therapy at the target lesions under general anesthesia. To evaluate the treatment outcome, serum prostate-specific antigen (PSA) levels were followed up in the 1st, 3rd, 6th, 9th, 12th months, and mpMRI was taken in the 1st and 12th months, followed by MR fusion biopsy in the 12th month post-IRE. Results: The mean age of the patients was 66.1 ± 9.3 with a median PSA of 7.5 ng/ml. After the treatment, PSA nadir was 4.06 ± 3.4, and 11 (64.7%) achieved decline of PSA more than 50% from the baseline. Rate of negative biopsy for prostate cancer is 88% (15/17) at 12 months MR fusion biopsy after the IRE treatment. Among the relapsed cases, 1 (6.9%) patient recurred at margin of treated area, and 1 (6.9%) patient was from outfield recurrence. When excluding initial four patients, none of the patients had cancer recur. Conclusions: When treating with IRE focal therapy, PSMA-PET CT is a potentially valuable diagnostic approach for localizing prostate cancer; it supports the detection of lesions with conventional mpMRI, enabling to perform the procedure more completely.

Automatic Lung Cancer Segmentation in [18F]FDG PET/CT Using a Two-Stage Deep Learning Approach.

Purpose: Since accurate lung cancer segmentation is required to determine the functional volume of a tumor in [18F]FDG PET/CT, we propose a two-stage U-Net architecture to enhance the performance of lung cancer segmentation using [18F]FDG PET/CT. Methods: The whole-body [18F]FDG PET/CT scan data of 887 patients with lung cancer were retrospectively used for network training and evaluation. The ground-truth tumor volume of interest was drawn using the LifeX software. The dataset was randomly partitioned into training, validation, and test sets. Among the 887 PET/CT and VOI datasets, 730 were used to train the proposed models, 81 were used as the validation set, and the remaining 76 were used to evaluate the model. In Stage 1, the global U-net receives 3D PET/CT volume as input and extracts the preliminary tumor area, generating a 3D binary volume as output. In Stage 2, the regional U-net receives eight consecutive PET/CT slices around the slice selected by the Global U-net in Stage 1 and generates a 2D binary image as the output. Results: The proposed two-stage U-Net architecture outperformed the conventional one-stage 3D U-Net in primary lung cancer segmentation. The two-stage U-Net model successfully predicted the detailed margin of the tumors, which was determined by manually drawing spherical VOIs and applying an adaptive threshold. Quantitative analysis using the Dice similarity coefficient confirmed the advantages of the two-stage U-Net. Conclusion: The proposed method will be useful for reducing the time and effort required for accurate lung cancer segmentation in [18F]FDG PET/CT.

Initial Experiences of Selective RET Inhibitor Selpercatinib in Adults with Metastatic Differentiated Thyroid Carcinoma and Medullary Thyroid Carcinoma: Real-World Case Series in Korea.

Recently, selpercatinib, a highly selective inhibitor of RET receptor tyrosine kinase, has been used for RET-altered thyroid cancer. We present four cases of patients with advanced thyroid cancer who were treated with selpercatinib. The first patient was a 63-year-old male with advanced medullary thyroid cancer (MTC) treated with vandetanib. Six months ago, he had an intracranial hemorrhage and swallowing difficulty. He started selpercatinib with percutaneous endoscopic gastrostomy (PEG). For 11 months, a partial response (PR) was observed stably with PEG administration without any more cardiovascular events. The second patient was a 67-year-old female with advanced MTC treated with vandetatib. After selpercatinib treatment, a PR was observed for most metastatic sites, including choroidal metastasis. The third patient was a 32-year-old female with advanced papillary thyroid cancer (PTC) without history of systematic treatment. For six months, a PR was observed at her metastatic site with manageable adverse events. The last patient was a 59-year-old female with advanced PTC treated with lenvatinib. She suffered from a panic disorder and pleural pain due to metastasis during lenvatinib treatment. After selpercatinib treatment, her pain and panic symptoms were improved. Facing varying clinical obstacles of the real world, selpercatinib safely proved remarkable therapeutic efficacy regardless of previous treatment or metastatic site.

A Single Dose of Novel PSMA-Targeting Radiopharmaceutical Agent [177Lu]Ludotadipep for Patients with Metastatic Castration-Resistant Prostate Cancer: Phase I Clinical Trial.

[177Lu]Ludotadipep, which enables targeted delivery of beta-particle radiation to prostate tumor cells, had been suggested as a promising therapeutic option for mCRPC. From November 2020 to March 2022, a total of 30 patients were enrolled for single dose of [177Lu]Ludotadipep RPT, 6 subjects in each of the 5 different activity groups of 1.9 GBq, 2.8 GBq, 3.7 GBq, 4.6 GBq, and 5.6 GBq. [177Lu]Ludotadipep was administered via venous injection, and patients were hospitalized for three days to monitor for any adverse effects. Serum PSA levels were followed up at weeks 1, 2, 3, 4, 6, 8, and 12, and PSMA PET/CT with [18F]Florastamin was obtained at baseline and again at weeks 4 and 8. The subjects required positive PSMA PET/CT prior to [177Lu]Ludotadipep administration. Among the 29 subjects who received [177Lu]Ludotadipep, 36 treatment emergent adverse events (TEAEs) occurred in 17 subjects (58.6%) and 4 adverse drug reactions (ADRs) in 3 subjects (10.3%). Of the total 24 subjects who had full 12-week follow-up data, 16 (66.7%) showed decrease in PSA of any magnitude, and 9 (37.5%) showed a decrease in PSA by 50% or greater. A total of 5 of the 24 patients (20.8%) showed disease progression (PSA increase of 25% or higher from the baseline) at the 12th week following single dose of [177Lu]Ludotadipep. These data thus far suggest that [177Lu]Ludotadipep could be a promising RPT agent with low toxicity in mCRPC patients who have not been responsive to conventional treatments.

Caudate-anchored cognitive connectivity pursuant to orthostatic hypotension in early Parkinson's disease.

18F-Florbetaben is a tracer used to evaluate the metabolic activity of and amyloid accumulation in the brain when measured in early- and late-phase, respectively. The metabolism of neural substrates could be viewed as a network and might be an important factor in cognition. Orthostatic hypotension (OH) might play an indirect moderating role in cognition, and its latent influence could modify the inherent cognitive network. This study aimed to identify changes of cognitive connectivity according to orthostatic stress in patients with early Parkinson's disease (PD). This study included 104 early PD patients who were evaluated with a head-up tilt-test and18F-Florbetaben positron emission tomography (PET). Cognition was assessed with a comprehensive neuropsychological battery that gauged attention/working memory, language, visuospatial, memory, and executive functions. PET images were analyzed visually for amyloid deposits, and early-phase images were normalized to obtain standardized uptake ratios (SUVRs) of pre-specified subregions relevant to specific cognitive domains. The caudate nucleus was referenced and paired to these pre-specified regions. The correlations between SUVRs of these regions were assessed and stratified according to presence of orthostatic hypotension. Among the patients studied, 22 (21.2%) participants had orthostatic hypotension. Nineteen patients (18.3%) were positive for amyloid-ß accumulation upon visual analysis. Moderate correlations between the caudate and pre-specified subregions were observed (Spearman's rho, range [0.331-0.545]). Cognition did not differ, but the patterns of correlation were altered when the disease was stratified by presence of orthostatic stress. In conclusion, cognition in early PD responds to hemodynamic stress by adapting its neural connections between regions relevant to cognitive functions.

Comparison of disease progression between brain-predominant Parkinson's disease versus Parkinson's disease with body-involvement phenotypes.

Recently, new disease phenotyping has been proposed based on the origin site of α-synuclein pathology in Parkinson's disease (PD). In addition, a great deal of evidences suggested of parallel degeneration in the central nervous system and peripheral nervous system in PD. The myocardial uptake pattern of 123I-meta-iodobenzylguanidine can be a surrogate imaging biomarker for the peripheral nervous system involvement in PD. This study aimed to compare the clinical progression between brain-predominant PD (br-PD) and PD with body-involvement (bo-PD) phenotypes according to the onset of cardiac sympathetic denervation (CSD); the bo-PD group was defined as having the early onset of CSD and the br-PD phenotype was defined as those without initial CSD but later developed CSD in subsequent scans (the delayed onset of CSD). Clinical chracteristics, dopamine transporter activity, and non-motor manifestations were compared between the groups. Motor symptoms and cognitive functions at the initial and follow-up tests [3.1 (±1.4) years interval] were compared between the groups. This study included 29 br-PD and 103 bo-PD patients. Symptoms of rapid-eye-movement sleep behavior disorder, excessive daytime sleepiness, constipation, and orthostatic hypotension were more frequent in the bo-PD than in the br-PD group. The Unified Parkinson's Disease Rating Scale part III score was higher at the initial and increased more steeply during the follow-up period in the bo-PD patients than in the br-PD patients. Although the general cognitive status was not much different between the groups at initial and follow-up, each group showed statistically different cognitive domain profiles and progression patterns. The results demonstrated that the bo-PD group had more severe initial symptoms and steeper motor deterioration than the br-PD group, which indicated that there may be the more pathological involvements of central and peripheral nervous systems in the bo-PD group.

18F-FES PET/CT for Characterization of Brain and Leptomeningeal Metastasis in Double Primary Cancer Patient.

ABSTRACT: The clinical value of 16α-18F-fluoro-17 ß-estradiol (18F-FES) PET in breast cancer has been widely investigated because it can visualize estrogen receptor-expressing lesions. This relatively new radiotracer adds clinical values by characterization of metastasis in double primary cancer. It also has advantage in finding small brain lesions, which has no background brain activity. Here, we present 18F-FES PET findings of brain and leptomeningeal metastases in a patient with breast and lung malignancy.

Characteristic functional cores revealed by hyperbolic disc embedding and k-core percolation on resting-state fMRI.

Hyperbolic disc embedding and k-core percolation reveal the hierarchical structure of functional connectivity on resting-state fMRI (rsfMRI). Using 180 normal adults' rsfMRI data from the human connectome project database, we visualized inter-voxel relations by embedding voxels on the hyperbolic space using the [Formula: see text] model. We also conducted k-core percolation on 30 participants to investigate core voxels for each individual. It recursively peels the layer off, and this procedure leaves voxels embedded in the center of the hyperbolic disc. We used independent components to classify core voxels, and it revealed stereotypes of individuals such as visual network dominant, default mode network dominant, and distributed patterns. Characteristic core structures of resting-state brain connectivity of normal subjects disclosed the distributed or asymmetric contribution of voxels to the kmax-core, which suggests the hierarchical dominance of certain IC subnetworks characteristic of subgroups of individuals at rest.

Development of Amyloid PET Analysis Pipeline Using Deep Learning-Based Brain MRI Segmentation-A Comparative Validation Study.

Amyloid positron emission tomography (PET) scan is clinically essential for the non-invasive assessment of the presence and spatial distribution of amyloid-beta deposition in subjects with cognitive impairment suspected to have been a result of Alzheimer's disease. Quantitative assessment can enhance the interpretation reliability of PET scan; however, its clinical application has been limited due to the complexity of preprocessing. This study introduces a novel deep-learning-based approach for SUVR quantification that simplifies the preprocessing step and significantly reduces the analysis time. Using two heterogeneous amyloid ligands, our proposed method successfully distinguished standardized uptake value ratio (SUVR) between amyloidosis-positive and negative groups. The proposed method's intra-class correlation coefficients were 0.97 and 0.99 against PETSurfer and PMOD, respectively. The difference of global SUVRs between the proposed method and PETSurfer or PMOD were 0.04 and -0.02, which are clinically acceptable. The AUC-ROC exceeded 0.95 for three tools in the amyloid positive assessment. Moreover, the proposed method had the fastest processing time and had a low registration failure rate (1%). In conclusion, our proposed method calculates SUVR that is consistent with PETSurfer and PMOD, and has advantages of fast processing time and low registration failure rate. Therefore, PET quantification provided by our proposed method can be used in clinical practice.

Comparison of FDG PET/CT and Bone Marrow Biopsy Results in Patients with Diffuse Large B Cell Lymphoma with Subgroup Analysis of PET Radiomics.

Whether FDG PET/CT can replace bone marrow biopsy (BMBx) is undecided in patients with diffuse large B cell lymphoma (DLBCL). We compared the visual PET findings and PET radiomic features, with BMBx results. A total of 328 patients were included; 269 (82%) were PET-negative and 59 (18%) were PET-positive for bone lesions on visual assessment. A fair degree of agreement was present between PET and BMBx findings (ĸ = 0.362, p < 0.001). Bone involvement on PET/CT lead to stage IV in 12 patients, despite no other evidence of extranodal lesion. Of 35 discordant PET-positive and BMBx-negative cases, 22 (63%) had discrete bone uptake on PET/CT. A total of 144 patients were eligible for radiomic analysis, and two grey-level zone-length matrix derived parameters obtained from the iliac crests showed a trend for higher values in the BMBx-positive group compared to the BMBx-negative group (mean 436.6 ± 449.0 versus 227.2 ± 137.8, unadjusted p = 0.037 for high grey-level zone emphasis; mean 308.8 ± 394.4 versus 135.7 ± 97.2, unadjusted p = 0.048 for short-zone high grey-level emphasis), but statistical significance was not found after multiple comparison correction. Visual FDG PET/CT assessment and BMBx results were discordant in 17% of patients with newly diagnosed DLBCL, and the two tests are complementary in the evaluation of bone involvement.

Hyperbolic disc embedding of functional human brain connectomes using resting-state fMRI.

The brain presents a real complex network of modular, small-world, and hierarchical nature, which are features of non-Euclidean geometry. Using resting-state functional magnetic resonance imaging, we constructed a scale-free binary graph for each subject, using internodal time series correlation of regions of interest as a proximity measure. The resulting network could be embedded onto manifolds of various curvatures and dimensions. While maintaining the fidelity of embedding (low distortion, high mean average precision), functional brain networks were found to be best represented in the hyperbolic disc. Using the 𝕊1/ℍ2 model, we reduced the dimension of the network into two-dimensional hyperbolic space and were able to efficiently visualize the internodal connections of the brain, preserving proximity as distances and angles on the hyperbolic discs. Each individual disc revealed relevance with its anatomic counterpart and absence of center-spaced node. Using the hyperbolic distance on the 𝕊1/ℍ2 model, we could detect the anomaly of network in autism spectrum disorder subjects. This procedure of embedding grants us a reliable new framework for studying functional brain networks and the possibility of detecting anomalies of the network in the hyperbolic disc on an individual scale.

Changes in treatment intent and target definition for preoperative radiotherapy after 18F-Fluorodeoxyglucose positron emission tomography in rectal cancer: A Meta-analysis.

PURPOSE: To evaluate the impact of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on changes in treatment plan and target definition for preoperative radiotherapy in patients with rectal cancer. METHODS: Embase, PubMed, and Cochrane Library were searched up to November 2020 for all studies investigating the role of preoperative FDG PET in patients who underwent neoadjuvant radiotherapy before curative-intent surgery. The proportion of patients whose treatment plan (curative vs. palliative intent) or target definition was changed after FDG PET was analyzed. A random-effects model was used for pooled analysis. The change in target definition was compared between conventional radiological imaging-based target volume [gross tumor volume (GTV) or planning target volume (PTV)] and PET-based target volume (GTV or PTV) using the standardized mean difference (SMD) and 95% confidence interval (CI). RESULTS: A total of 336 patients from twelve studies were included. In eight studies, PET changed either the treatment intent or target definition in 24.8% of patients (95% CI 15.1% to 37.9%, I2 = 69%). In ten studies, the PET-based GTV was lower than the conventional imaging-based target volume (SMD -7.0, 95% CI -1.39 to -0.01). However, there was no significant difference between conventional imaging-based and PET-based PTV (SMD -0.07, 95% CI -0.75 to 0.62). In six studies evaluating the initial staging based on PET, the initial staging (nodal or metastasis status) was changed in 53 of 229 patients (23.1%). Newly detected or additional distant metastases were identified in 22 patients (9.6%) after FDG PET. CONCLUSION: The use of FDG PET influences radiotherapy planning in a fourth of patients with rectal cancer. FDG PET can provide additive information for accurate tumor delineation, although PET-based PTV did not significantly change. These findings suggest that FDG PET may be beneficial to patients with rectal cancer before establishing a radiotherapy plan.