Improving diagnostic precision in amyloid brain PET imaging through data-driven motion correction.

BACKGROUND: Head motion during brain positron emission tomography (PET)/computed tomography (CT) imaging degrades image quality, resulting in reduced reading accuracy. We evaluated the performance of a head motion correction algorithm using 18F-flutemetamol (FMM) brain PET/CT images. METHODS: FMM brain PET/CT images were retrospectively included, and PET images were reconstructed using a motion correction algorithm: (1) motion estimation through 3D time-domain signal analysis, signal smoothing, and calculation of motion-free intervals using a Merging Adjacent Clustering method; (2) estimation of 3D motion transformations using the Summing Tree Structural algorithm; and (3) calculation of the final motion-corrected images using the 3D motion transformations during the iterative reconstruction process. All conventional and motion-corrected PET images were visually reviewed by two readers. Image quality was evaluated using a 3-point scale, and the presence of amyloid deposition was interpreted as negative, positive, or equivocal. For quantitative analysis, we calculated the uptake ratio (UR) of 5 specific brain regions, with the cerebellar cortex as a reference region. The results of the conventional and motion-corrected PET images were statistically compared. RESULTS: In total, 108 sets of FMM brain PET images from 108 patients (34 men and 74 women; median age, 78 years) were included. After motion correction, image quality significantly improved (p < 0.001), and there were no images of poor quality. In the visual analysis of amyloid deposition, higher interobserver agreements were observed in motion-corrected PET images for all specific regions. In the quantitative analysis, the UR difference between the conventional and motion-corrected PET images was significantly higher in the group with head motion than in the group without head motion (p = 0.016). CONCLUSIONS: The motion correction algorithm provided better image quality and higher interobserver agreement. Therefore, we suggest that this algorithm be adopted as a routine post-processing protocol in amyloid brain PET/CT imaging and applied to brain PET scans with other radiotracers.

Cerebrovascular Malformation Mimicking Recurrent Lymphoma on Dual Time-Point 18F-FDOPA PET.

ABSTRACT: Although 18F-FDG is the dominant radiotracer for PET imaging of hematological malignancies, radiolabeled amino acids have also been investigated to improve image quality in areas of high 18F-FDG uptake such as the central nervous system. We present a case of a 57-year-old woman who underwent an 18F-FDOPA scan for primary CNS lymphoma, which demonstrated an unexpected false-positive uptake in the right frontal lobe, due to a developmental venous anomaly.

The two-back task leads to activity in the left dorsolateral prefrontal cortex in schizophrenia patients with predominant negative symptoms: a fNIRS study and its implication for tDCS.

Transcranial direct current stimulation (tDCS) over left dorsolateral prefrontal cortex (DLPFC) has shown some potential as an adjunctive intervention for ameliorating negative symptoms of schizophrenia, but its efficacy requires optimization. Recently, 'functional targeting' of stimulation holds promise for advancing tDCS efficacy by coupling tDCS with a cognitive task where the target brain regions are activated by that task and further specifically polarized by tDCS.The study used 48-channel functional near infra-red spectroscopy (fNIRS) aiming to determine a cognitive task that can effectively induce a cortical activation of the left DLPFC in schizophrenia patients with predominant negative symptoms before running a tDCS trial. Sixty schizophrenia patients with predominant negative symptoms completed measures of clinical and psychosocial functioning characteristics and assessments across cognitive domains. Hemodynamic changes during n-back working memory tasks with different cognitive loads (1-back and 2-back) and verbal fluency test (VFT) were measured using fNIRS. For n-back tasks, greater signal changes were found when the task required elevated cognitive load. One sample t-test revealed that only 2-back task elicited significant activation in left DLPFC (t = 4.23, FDR-corrected p = 0.0007). During VFT, patients failed to show significant task-related activity in left DLPFC (one sample t-test, t = -0.25, FDR-corrected p > 0.05). Our study implies that 2-back task can effectively activate left DLPFC in schizophrenia patients with predominant negative symptoms. This neurophysiologically-validated task is considered highly potential to be executed in conjunction with high-definition tDCS for "functional targeting" of the left DLPFC to treat negative symptoms in a double-blind randomized sham-control trial, registered on ClinicalTrials.gov Registry (ID: NCT05582980).

Clinical Challenge of Two Competing Targetable Mutations in Non-Small-Cell Lung Cancer: A Case Report.

The development of therapeutic agents targeting products of epidermal growth factor receptor (EGFR) gene mutation and anaplastic lymphoma kinase (ALK) rearrangements has improved survival in patients with non-small-cell lung cancer. EGFR and ALK mutations are generally regarded as mutually exclusive, and the presence of one in lieu of another influences the response to targeted therapy. We herein present an interesting case following the course of progression of a patient with synchronous lung cancers with a discordant mutation profile. The importance of this modality in the follow-up of lung cancer patients is illustrated, and the therapeutic implications of coexisting oncogenic drivers are briefly discussed.

Resting-State EEG Connectivity at High-Frequency Bands and Attentional Performance Dysfunction in Stabilized Schizophrenia Patients.

Background and Objectives: Attentional dysfunction has long been viewed as one of the fundamental underlying cognitive deficits in schizophrenia. There is an urgent need to understand its neural underpinning and develop effective treatments. In the process of attention, neural oscillation has a central role in filtering information and allocating resources to either stimulus-driven or goal-relevant objects. Here, we asked if resting-state EEG connectivity correlated with attentional performance in schizophrenia patients. Materials and Methods: Resting-state EEG recordings were obtained from 72 stabilized patients with schizophrenia. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity between 84 intra-cortical current sources determined by eLORETA (exact low-resolution brain electromagnetic tomography) for five frequencies. The Conners' Continuous Performance Test-II (CPT-II) was administered for evaluating attentional performance. Linear regression with a non-parametric permutation randomization procedure was used to examine the correlations between the whole-brain functional connectivity and the CPT-II measures. Results: Greater beta-band right hemispheric fusiform gyrus (FG)-lingual gyrus (LG) functional connectivity predicted higher CPT-II variability scores (r = 0.44, p < 0.05, corrected), accounting for 19.5% of variance in the CPT-II VAR score. Greater gamma-band right hemispheric functional connectivity between the cuneus (Cu) and transverse temporal gyrus (TTG) and between Cu and the superior temporal gyrus (STG) predicted higher CPT-II hit reaction time (HRT) scores (both r = 0.50, p < 0.05, corrected), accounting for 24.6% and 25.1% of variance in the CPT-II HRT score, respectively. Greater gamma-band right hemispheric Cu-TTG functional connectivity predicted higher CPT-II HRT standard error (HRTSE) scores (r = 0.54, p < 0.05, corrected), accounting for 28.7% of variance in the CPT-II HRTSE score. Conclusions: Our study indicated that increased right hemispheric resting-state EEG functional connectivity at high frequencies was correlated with poorer focused attention in schizophrenia patients. If replicated, novel approaches to modulate these networks may yield selective, potent interventions for improving attention deficits in schizophrenia.

Prognostic value of TLR from FDG PET/CT in patients with margin-negative stage IB and IIA non-small cell lung cancer.

OBJECTIVES: To evaluate the prognostic value of TLR from PET/CT in patients with resection margin-negative stage IB and IIA non-small cell lung cancer (NSCLC) and compare high-risk factors necessitating adjuvant treatment (AT). METHODS: Consecutive FDG PET/CT scans performed for the initial staging of NSCLC stage IB and IIA were retrospectively reviewed. The maximum standardized uptake value (SUVmax) of the primary tumor and mean SUV of the liver were acquired. The tumor-to-liver SUV ratio (TLR) was also calculated. Charts were reviewed for basic patient characteristics and high-risk factors for considering AT (poor differentiation, visceral pleura invasion, vascular invasion, tumors > 4 cm, and wedge resection). Statistical analysis was performed using Cox regression analysis and the Kaplan-Meier method. RESULTS: Of the 112 patients included, 15 (13.4%) died, with a median overall survival (OS) of 43.8 months. Twenty-two patients (19.6%) exhibited recurrence, with median disease-free survival (DFS) of 36.0 months. In univariable analysis, pathology, poor differentiation, and TLR were associated with shorter DFS and OS. In multivariable analysis, TLR (hazard ratio [HR] = 1.263, p = 0.008) and differentiation (HR = 3.087, p = 0.012) were associated with shorter DFS. Also, TLR (HR = 1.422, p < 0.001) was associated with shorter OS. CONCLUSION: TLR from FDG PET/CT was an independent prognostic factor for recurrence and survival. PET parameters constitute risk factors for consideration in the decision-making for AT in margin-negative stage IB and IIA NSCLC. CLINICAL RELEVANCE STATEMENT: In this study, TLR from FDG PET/CT was an independent prognostic factor in stage IB-IIA non-small cell cancer patients. Although additional validation studies are warranted, TLR has the potential to be used to determine the need for adjuvant therapy. KEY POINTS: • High TLR is an independent poor prognostic factor in stage IB-IIA NSCLC. • Adjuvant treatment should be considered in patients with high TLR following complete tumor resection.

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.

Relationship between Systemic Inflammatory Markers, GLUT1 Expression, and Maximum 18F-Fluorodeoxyglucose Uptake in Non-Small Cell Lung Carcinoma and Their Prognostic Significance.

BACKGROUND: Factors involved in inflammation and cancer interact in various ways with each other, and biomarkers of systemic inflammation may have a prognostic value in cancer. Glucose transporter 1 (GLUT1) plays a pivotal role in glucose transport and metabolism and it is aberrantly expressed in various cancer types. We evaluated the differential expression of GLUT1, along with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in non-small-cell lung cancer (NSCLC), and then analyzed their prognostic significance. METHODS: A total of 163 patients with resectable NSCLC were included in this study. Tumor sections were immunohistochemically stained for GLUT1 and GLUT3. Maximum standardized uptake value (SUVmax) was measured by preoperative FDG-PET, and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) were derived from pretreatment blood count. RESULTS: GLUT1 and GLUT3 was positively expressed in 74.8% and 6.1% of the NSCLC tissues, respectively. GLUT1 expression was significantly correlated with squamous cell carcinoma histology, poor differentiation, high pathologic stage, old age, male, smoking, and high SUVmax (>7) (all p < 0.05). The squamous cell carcinoma and smoker group also showed significantly higher SUVmax (both p < 0.001). Systemic inflammation markers, including NLR, PLR, and LMR, were positively correlated with high SUVmax (all p < 0.05). High GLUT1 expression, high SUVmax, high NLR, and low LMR, were significantly associated with poor overall survival in patients with NSCLC. However, in the multivariate survival analysis, LMR was an independent prognostic factor overall (HR 1.86, 95% CI 1.05-3.3) and for the stage I/II cohort (HR 2.3, 95% CI 1.24-4.3) (all p < 0.05). CONCLUSIONS: Systemic inflammatory markers-NLR, PLR, and LMR are strongly correlated with the SUVmax and are indicators of aggressive tumor behavior. Specifically, LMR is a promising prognostic biomarker in NSCLC patients.

Online Left-Hemispheric In-Phase Frontoparietal Theta tACS Modulates Theta-Band EEG Source-Based Large-Scale Functional Network Connectivity in Patients with Schizophrenia: A Randomized, Double-Blind, Sham-Controlled Clinical Trial.

EEG studies indicated that schizophrenia patients had increased resting-state theta-band functional connectivity, which was associated with negative symptoms. We recently published the first study showing that theta (6 Hz) transcranial alternating current stimulation (tACS) over left prefrontal and parietal cortices during a working memory task for accentuating frontoparietal theta-band synchronization (in-phase theta-tACS) reduced negative symptoms in schizophrenia patients. Here, we hypothesized that in-phase theta-tACS can modulate theta-band large-scale networks connectivity in schizophrenia patients. In this randomized, double-blind, sham-controlled trial, patients received twice-daily, 2 mA, 20-min sessions of in-phase theta-tACS for 5 consecutive weekdays (n = 18) or a sham stimulation (n = 18). Resting-state electroencephalography data were collected at baseline, end of stimulation, and at one-week follow-up. Exact low resolution electromagnetic tomography (eLORETA) was used to compute intra-cortical activity. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity across 84 cortical regions at theta frequency (5-7 Hz). EEG data from 35 patients were analyzed. We found that in-phase theta-tACS significantly reduced the LPS between the posterior cingulate (PC) and the parahippocampal gyrus (PHG) in the right hemisphere only at the end of stimulation relative to sham (p = 0.0009, corrected). The reduction in right hemispheric PC-PHG LPS was significantly correlated with negative symptom improvement at the end of the stimulation (r = 0.503, p = 0.039). Our findings suggest that in-phase theta-tACS can modulate theta-band large-scale functional connectivity pertaining to negative symptoms. Considering the failure of right hemispheric PC-PHG functional connectivity to predict improvement in negative symptoms at one-week follow-up, future studies should investigate whether it can serve as a surrogate of treatment response to theta-tACS.

Prognostic impact of 18F-FDG PET/CT in pathologic stage II invasive ductal carcinoma of the breast: re-illuminating the value of PET/CT in intermediate-risk breast cancer.

BACKGROUND: The aim of this study is to investigate the impact of 18F-FDG PET/CT on prognosis of stage II invasive ductal carcinoma (IDC) of the breast primarily treated with surgery. METHODS: The clinical records of 297 consecutive IDC with preoperative PET/CT and pathologically staged II in surgery from 2013 to 2017 were retrospectively reviewed. The maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), tumor-to-liver ratio (TLR), and metabolic tumor volume (MTV) were measured. Association of clinicopathologic factors (age, T stage, N stage, AJCC pathologic stage of IIA or IIB, pathologic prognostic stage, grade, hormonal receptor status, HER2 status, Ki-67, and adjuvant therapy) and PET parameters with DFS was assessed using the Cox proportional hazards model. RESULTS: There were 35 recurrences and 10 deaths at a median follow-up of 49 months (range 0.8 ~ 87.3). All PET parameters were significantly associated with DFS in univariate analysis but in multivariate analysis, SUVpeak was the only factor significantly associated with DFS (hazard ratio 2.58, 95% confidence interval 1.29-5.15, P = 0.007). In cohorts with higher values of SUVpeak or TLR, patients who received adjuvant chemotherapy had significantly superior DFS. CONCLUSION: Metabolic parameters derived from preoperative PET/CT was significantly associated with recurrence in stage II IDC primarily treated with surgery. PET/CT can be a powerful prognostic tool in conjunction with novel staging systems and current biomarkers for patients undergoing contemporary therapy. Our results urge to reconsider the currently underestimated value of PET/CT confined to diagnostic aspect and to newly recognize its prognostic impact in these intermediate-risk breast cancer.

Brown fat activation demonstrated on FDG PET/CT predicts survival outcome.

PURPOSE: The purpose of this study was to compare the survival of patients with and without BAT activity on FDG PET/CT. METHODS: PET/CT exams from 3937 breast cancer patients were retrospectively reviewed for bilateral symmetric elongated FDG activity in the neck and chest, typical of BAT activation. A control group of age-matched (± 1 year) breast cancer patients who underwent PET/CT the same week was also enrolled for comparison. Kaplan-Meier curves of progression-free survival (PFS) and overall survival (OS) for BAT positive patients and the control group were calculated. Further sub-analysis was performed to account for the hormonal changes associated with menopause. RESULTS: 2.0% (80/3937) of the breast cancer patients who underwent PET/CT demonstrated BAT activation, and 80 additional patients were analyzed for comparison as the group without BAT activity. Mean follow-up was 76 months (range 1-225 months). There were 4 recurrences in the BAT group, compared to 12 in the control. The mean PFS for the BAT group was 127 months, which was significantly lower than the mean PFS of 180 months in the control (p = 0.047). Sub-analysis of premenopausal women again showed longer PFS for the BAT group (129 vs. 196 months, p = 0.095) while no difference was found in postmenopausal women (mean 102 vs. 135 months, p = 0.360). Presence of BAT activity was also a significant predictor variable for PFS on Cox regression. CONCLUSION: Patients with BAT activity showed longer progression-free survival than those without, emphasizing the need for further evaluation of its role in metabolism, treatment response, tumor microenvironment and long-term prognosis.

Clinical conditions related to positive thymic uptake on I-131 post-therapeutic scans in thyroid cancer patients.

OBJECTIVE: Thymic uptake is a well-known cause of false-positives on I-131 post-therapeutic scans. This study identified the clinical conditions associated with thymic uptake on I-131 post-therapeutic scans in thyroid cancer patients. DESIGN: This was a retrospective study that investigated the clinical conditions associated with thymic uptake on I-131 post-therapeutic scans of patients obtained between January 2010 and December 2010. PATIENTS: Six hundred and eighty-five patients were included follwing a therapeutic dose of I-131 (3.7-9.25 GBq). METHODS: We reviewed the patients' clinical characteristics, including age, sex, histology, serum thyrotropin (TSH) stimulation regimen, prior history of RAI therapy, and labaratory parameters such as the serumTSH, thyroglobulin, and anti-thyroglobulin antibody. At follow-up, patients were assessed in terms of disease-free status, structural persistence, and biochemical disease. RESULTS: In total, 107 I-131 post-therapeutic scans (15.6%) evidenced thymic uptake. The mean age of the positive thymic uptake group was significantly lower than that of the negative group (p < .001). Significant indicators for thymic uptake were thyroid hormone withdrawal and a history of repeated radioactive iodine (RAI) therapy (p < .05). Logistic regression analysis showed that young age and a history of repeated RAI therapy correlated with thymic uptake (p < .001). At the end of follow-up, 487 patients (86.5%) were disease-free, 44 (7.8%) still had biochemical disease, and 32 (5.7%) showed structural persistence. Ten patients (11.5%) in the positive thymic uptake group and 22 (4.6%) in the negative thymic uptake group showed structural persistence. Five patients (5.7%) in the positive thymic uptake group and 39 (8.2%) in the negative thymic uptake group had biochemical disease. The final follow-up results of the two groups were statistically different. CONCLUSIONS: Thymic uptake tended to be more prominent in young patients with a history of repeated RAI therapy. Structural recurrence during follow-up was much more common in the positive thymic uptake group, while the incidence of biochemical recurrence during follow-up was higher in the negative thymic uptake group.

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.

Prognostic value of tumor metabolic imaging phenotype by FDG PET radiomics in HNSCC.

OBJECTIVE: Tumor metabolic phenotype can be assessed with integrated image pattern analysis of 18F-fluoro-deoxy-glucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT), called radiomics. This study was performed to assess the prognostic value of radiomics PET parameters in head and neck squamous cell carcinoma (HNSCC) patients. METHODS: 18F-fluoro-deoxy-glucose (FDG) PET/CT data of 215 patients from HNSCC collection free database in The Cancer Imaging Archive (TCIA), and 122 patients in Seoul St. Mary's Hospital with baseline FDG PET/CT for locally advanced HNSCC were reviewed. Data from TCIA database were used as a training cohort, and data from Seoul St. Mary's Hospital as a validation cohort. With the training cohort, primary tumors were segmented by Nestles' adaptive thresholding method. Segmental tumors in PET images were preprocessed using relative resampling of 64 bins. Forty-two PET parameters, including conventional parameters and texture parameters, were measured. Binary groups of homogeneous imaging phenotypes, clustered by K-means method, were compared for overall survival (OS) and disease-free survival (DFS) by log-rank test. Selected individual radiomics parameters were tested along with clinical factors, including age and sex, by Cox-regression test for OS and DFS, and the significant parameters were tested with multivariate analysis. Significant parameters on multivariate analysis were again tested with multivariate analysis in the validation cohort. RESULTS: A total of 119 patients, 70 from training, and 49 from validation cohort, were included in the study. The median follow-up period was 62 and 52 months for the training and the validation cohort, respectively. In the training cohort. binary groups with different metabolic radiomics phenotypes showed significant difference in OS (p = 0.036), and borderline difference in DFS (p = 0.086). Gray-Level Non-Uniformity for zone (GLNUGLZLM) was the most significant prognostic factor for both OS (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.4-7.3, p = 0.008) and DFS (HR 4.5, CI 1.3-16, p = 0.020). Multivariate analysis revealed GLNUGLZLM as an independent prognostic factor for OS (HR 3.7, 95% CI 1.1-7.5, p = 0.032). GLNUGLZLM remained as an independent prognostic factor in the validation cohort (HR 14.8. 95% CI 3.3-66, p < 0.001). CONCLUSIONS: Baseline FDG PET radiomics contain risk information for survival prognosis in HNSCC patients. The metabolic heterogeneity parameter, GLNUGLZLM, may assist clinicians in patient risk assessment as a feasible prognostic factor.

Differences in cortical structure between cognitively normal East Asian and Caucasian older adults: a surface-based morphometry study.

There is a growing literature on the impact of ethnicity on brain structure and function. Despite the regional heterogeneity in age-related changes and non-uniformity across brain morphometry measurements in the aging process, paucity of studies investigated the difference in cortical anatomy between the East Asian and Caucasian older adults. The present study aimed to compare cortical anatomy measurements, including cortical thickness, volume and surface area, between cognitively normal East Asian (n = 171) and Caucasian (n = 178) older adults, using surface-based morphometry and vertex-wise group analysis of high-dimensional structural magnetic resonance imaging (MRI) data. The East Asian group showed greater cortical thickness and larger cortical volume in the right superior temporal gyrus, postcentral gyrus, bilateral inferior temporal gyrus, and inferior parietal cortex. The Caucasian group showed thicker and larger cortex in the left transverse temporal cortex, lingual gyrus, right lateral occipital cortex, and precentral gyrus. Additionally, the difference in surface area was discordant with that in cortical thickness. Differences in brain structure between the East Asian and Caucasian might reflect differences in language and information processing, but further studies using standardized methods for assessing racial characteristics are needed. The research results represent a further step towards developing a comprehensive understanding of differences in brain structure between ethnicities of older adults, and this would enrich clinical research on aging and neurodegenerative diseases.

Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-glutamate (18F-FSPG) for PET/CT Imaging in Patients with Newly Diagnosed and Recurrent Prostate Cancer.

PURPOSE: (4S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid (18F-FSPG) is a radiopharmaceutical for PET imaging of system xC - activity, which can be upregulated in prostate cancer. We present data on the first evaluation of patients with newly diagnosed or recurrent prostate cancer with this radiopharmaceutical. EXPERIMENTAL DESIGN: Ten patients with primary and 10 patients with recurrent prostate cancer were enrolled in this prospective multicenter study. After injection of 300 MBq of 18F-FSPG, three whole-body PET/CT scans were obtained. Visual analysis was compared with step-section histopathology when available as well as other imaging studies and clinical outcomes. Metabolic parameters were measured semiquantitatively. Expression levels of xCT and CD44 were evaluated by IHC for patients with available tissue samples. RESULTS: 18F-FSPG PET showed high tumor-to-background ratios with a relatively high tumor detection rate on a per-patient (89%) and per-lobe (87%) basis. The sensitivity was slightly higher with imaging at 105 minutes in comparison with 60 minutes. The maximum standardized uptake values (SUVmax) for cancer was significantly higher than both normal (P < 0.005) and benign pathology (P = 0.011), while there was no significant difference between normal and benign pathology (P = 0.120). In the setting of recurrence, agreement with standard imaging was demonstrated in 7 of 9 patients (78%) and 13 of 18 lesions (72%), and revealed true local recurrence in a discordant case. 18F-FSPG accumulation showed moderate correlation with CD44 expression. CONCLUSIONS: 18F-FSPG is a promising tumor imaging agent for PET that seems to have favorable biodistribution and high cancer detection rate in patients with prostate cancer. Further studies are warranted to determine the diagnostic value for both initial staging and recurrence, and how it compares with other investigational radiotracers and conventional imaging modalities.

Role of F-18 FDG PET/CT in non-conjunctival origin ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphomas.

BACKGROUND: Despite the widespread use of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in the diagnosis and response assessment of patients with lymphoma, few studies have assessed its value in ocular adnexal lymphomas. The purpose of this study was to evaluate the role of FDG PET/CT in staging of non-conjunctival origin ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphomas (OAML). In addition, the diagnostic sensitivity of FDG PET/CT was compared with magnetic resonance imaging (MRI). FDG PET/CT of 123 consecutive patients with pathologically proven OAML between January 2009 and February 2016 were retrospectively reviewed. The patients with MALT lymphoma originating from conjunctiva were excluded. A total 50 patients with non-conjunctival origin OAML were assessed. Maximum standardized uptake value (SUVmax) and additional PET parameters were measured for all lesions. Sensitivity for primary tumor detection was compared with MRI. RESULTS: Ten patients had bilateral OAML and total 60 OAML lesions were analyzed. MRI was missing in one patient. The tumor locations were as follows: eyelid, 9; lacrimal gland, 18; orbit, 33. Fifty lesions (83.3%) were FDG-avid tumors with mean ± SD SUVmax 4.8 ± 2.4 (range 2.0~11.1). The mean SUVmax according to tumor location were as follows: eyelid, 3.7 ± 1.1 (2.8~5.3); lacrimal gland, 3.6 ± 1.4 (2.1~6.4); orbit, 5.7 ± 2.6 (2.0~11.1). Mean SUVmax among the 3 locations were statistically different (P = 0.010). The sensitivity was calculated as 83.1% (49/59) for FDG PET/CT and 89.8% (53/59) for MRI, which were statistically comparable (P = 0.219 by McNemar's test). Seven of 50 patients (14%) were upstaged by detection of extraocular lesions by FDG PET/CT (1 kidney and lung, 1 tonsil, 4 cervical LNs, 1 sacral foramen). CONCLUSION: 83.3% of the non-conjunctival origin OAML were FDG-avid tumors, with FDG PET/CT showing comparable sensitivity to that of MRI. FDG PET/CT detected unsuspected extraocular lymphoma involvement in 14% of the patients. FDG PET/CT performed for staging of non-conjunctival origin OAML may thus guide therapeutic management.

Initial experience with a PET/computed tomography system using silicon photomultiplier detectors.

PURPOSE: A PET/computed tomography (CT) that uses silicon photomultiplier (SiPM) technology was installed at our institution. Here, we report the initial use of the new scanner and evaluate the image quality in comparison to standard PET/CT scanners. PROCEDURES: Seventy-two patients were scanned first using standard PET/CT followed immediately by the new PET/CT system. Images from the new PET/CT system were reconstructed using a conventional [non time-of-flight (TOF)] algorithm, TOF alone and TOF in combination with BSREM. Images from standard PET/CT were reconstructed using clinical standard-of-care settings. Three blinded readers randomly reviewed four datasets (standard, non-TOF, TOF alone, TOF+BSREM) per patient for image quality using a five-point Likert scale. SUV measurements for the single most avid lesion on each dataset were also recorded. RESULTS: Datasets from the new scanner had higher image quality (P < 0.001) and SUV measurements (P < 0.001) compared with the standard scanners, and scores further improved when TOF and BSREM algorithms were added (mean scores for standard, non-TOF, TOF alone and TOF+BSREM were 3.1, 3.9, 4.3 and 5.0, respectively; mean SUVmax for hottest lesion were 8.8, 10.3, 10.7 and 13.3, respectively). CONCLUSION: The SiPM-based PET/CT system outperforms two standard Bismuth germanium oxide- and Lutetium-yttrium oxyorthosilicate-based scanners in terms of image quality, with further benefits added using TOF and BSREM. This may be beneficial for detecting small lesions and more accurate disease staging.

Does FDG PET/CT have a role in determining adjuvant chemotherapy in surgical margin-negative stage IA non-small cell lung cancer patients?

PURPOSE: To evaluate the prognostic value of FDG PET/CT metabolic parameter compared to clinico-pathological risk factors in surgical margin-negative stage IA non-small cell lung cancer (NSCLC) patients. METHODS: 167 patients with consecutive FDG PET/CT scans from 2009 to 2015 performed for staging of NSCLC stage IA with plans for curative surgery were retrospectively reviewed. Maximum standardized uptake value (SUVmax) of primary tumor and mean SUV of liver were acquired from PET/CT. Tumor-to-liver SUV ratio (TLR) was calculated. Charts were reviewed to obtain basic patient characteristics (age, sex, smoking history, LDH, histologic subtype) and high-risk factors for adjuvant chemotherapy (tumor size, poorly differentiation, vascular invasion, and sub-lobar resection). Patients were dichotomized into two groups using optimal cut-off from receiver operating characteristic curve analysis of TLR to predict recurrence. Statistical analysis was done using Cox regression analysis and Kaplan-Meier method. Factors with P < 0.2 in univariate analysis were included in multivariate analysis. RESULTS: Recurrence rate was 12.6% (21/167). Median disease-free survival (DFS) was 47.2 months while 2-year and 5-year DFS rates were 93% and 86%, respectively. The optimal cut-off for TLR was 2.3. In univariate analysis, P value of sex, vascular invasion, and TLR were less than 0.2. In multivariable analysis, high TLR was the only factor that showed significant association with tumor recurrence (hazard ratio 3.795, P = 0.0048). CONCLUSIONS: TLR was an independent prognostic factor for recurrence and TLR could be an important risk factor to be considered in decision-making for adjuvant chemotherapy, even for those with stage IA NSCLC.

18F-florbetaben whole-body PET/MRI for evaluation of systemic amyloid deposition.

BACKGROUND: Florbetaben, a 18F-labeled stilbene derivative (Neuraceq®, formerly known as BAY-949172), is a diagnostic radiopharmaceutical developed to visualize ß-amyloid plaques in the brain. Here, we report a pilot study evaluating patients with suspected cardiac amyloidosis for systemic extent of disease. METHODS: We prospectively enrolled nine patients, 61-86 year old (mean ± SD 69.4 ± 8.6), referred from the cardiac amyloid clinic. First, dynamic imaging of the heart was acquired immediately after injection of 222-318.2 MBq (mean ± SD 270.1 ± 33.3) of 18F-florbetaben using the GE SIGNA PET/MRI. This was followed by a whole-body PET/MRI scan 60-146.4 min (mean ± SD 98 ± 33.4) after injection. Cardiac MRI sequences included ECG-triggered cine SSFP, T2-weighted, and late gadolinium-enhanced imaging. Whole-body MRI sequences included MRAC and axial T1-weighted imaging. RESULTS: High early uptake and delayed high uptake in the left ventricle correlated with amyloid deposition in five patients, while low uptake on early and delayed cardiac imaging was noted in four patients. Cardiac function measurements were successfully obtained in all participants. Areas of increased abnormal 18F-florbetaben accumulation were noted on delayed whole-body imaging in the bone marrow (seven patients), stomach (diffuse in five patients and focal in one patient), brain (five patients), salivary glands (three patients), tongue (three patients), spleen (three patients), skeletal muscles (three patients), ocular muscles (two patients), thyroid (two patients), pleura (two patients), kidneys (two patients), and lungs (two patients). CONCLUSIONS: Whole-body 18F-florbetaben PET/MRI is promising for localization of systemic amyloid deposition. This technique may provide important structural and functional information regarding the organs involved by disease, with potential to guide biopsy and evaluate response to treatment. TRIAL REGISTRATION: Clinicaltrials.gov registration: NCT03119558 .