Prognostic significance of pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with T2N1 hormone receptor-positive, ERBB2-negative breast cancer who underwent adjuvant chemotherapy.

PURPOSE: To determine whether tumor uptake of 18F-fluorodeoxyglucose (18F-FDG) is associated with invasive disease-free survival (IDFS) in patients with hormone receptor (HR)-positive ERBB2-negative early-stage breast cancer treated with adjuvant chemotherapy. METHODS: This is a single-center cohort study of women with breast cancer who underwent surgery between 2008 and 2015 at Asan Medical Center, Seoul, Korea. Patients were enrolled if they were diagnosed with HR-positive ERBB2-negative breast cancer with histology of invasive ductal carcinoma, had an American Joint Committee on Cancer pathologic tumor stage of T2N1 with 1-3 positive axillary nodes, underwent preoperative 18F-FDG positron emission tomography/computed tomography (PET/CT), and underwent breast cancer surgery followed by anthracycline- or taxane-based adjuvant chemotherapy. The primary outcome measure was IDFS. The maximum standardized uptake value (SUVmax) was dichotomized using a predefined cut-off of 4.14. RESULTS: A total of 129 patients were included. The median follow-up period for IDFS in those without recurrence was 82 months (interquartile range, 65-106). Multivariable Cox analysis showed that SUVmax was independently associated with IDFS [adjusted hazard ratio 2.49; 95% confidence interval (CI), 1.06-5.84]. Ten-year IDFS estimates via the Kaplan-Meier method were 0.60 (95% CI, 0.42-0.74) and 0.82 (95% CI, 0.65-0.91) for high and low SUVmax groups, respectively. The overall association between SUVmax and IDFS appeared to be consistent across subgroups divided according to age, progesterone receptor status, histologic grade, or presence of lymphovascular invasion. CONCLUSION: High SUVmax on preoperative 18F-FDG PET/CT was independently associated with reduced long-term IDFS in T2N1 HR-positive ERBB2-negative breast cancer patients who underwent adjuvant chemotherapy.

Retinal Thickness and Its Interocular Asymmetry Between Parkinson's Disease and Drug-Induced Parkinsonism.

BACKGROUND: Drug-induced parkinsonism (DIP) is common, but diagnosis is challenging. Although dopamine transporter imaging is useful, the cost and inconvenience are problematic, and an easily accessible screening technique is needed. We aimed to determine whether optical coherence tomography (OCT) findings could differentiate DIP from Parkinson's disease (PD). METHODS: We investigated 97 de novo PD patients and 27 DIP patients using OCT and [18F] N-(3-fluoropropyl)-2b-carbon ethoxy-3b-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography. We compared peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular retinal thickness (mRT) between PD and DIP patients as well as interocular differences in the pRNFLT and the mRT. Asymmetric index (%) for retinal thickness (AIRT) was calculated to measure the interocular differences between pRNFLT and mRT. The correlation between AIRT and total striatal specific/non-specific binding ratio asymmetry index (SNBRAI) was investigated in PD and DIP patients. RESULTS: No significant differences in pRNFLT and mRT values were observed between PD and DIP patients (all P values > 0.090). The mean SNBRAI was significantly higher in PD than in DIP (P = 0.008) patients; however, AIRT did not differ between PD and DIP patients in pRNFLT and mRT (all P values > 0.100). SNBRAI did not correlate with AIRT of pRNFL or mRT in PD and DIP patients (all P values > 0.060). CONCLUSION: Our study showed no benefit of retinal thickness and interocular asymmetry measurements using OCT for distinguishing PD from DIP in the early stages. Additional investigations are needed for confirmation.

Correlations with REM sleep behavior disorder severity in isolated rapid eye movement sleep behavior disorders patients.

OBJECTIVES: The pathogenesis of isolated rapid eye movement sleep behavior disorders (iRBD) is poorly understood. The severity of RBD may reflect its pathogenesis. METHODS: We compared motor function and non-motor symptoms (NMSs) between iRBD patients and healthy volunteers. We correlated motor function, NMSs, and striatal dopaminergic activity with RBD severity using video-polysomnography. RESULTS: Twenty-one iRBD patients and 17 controls participated. The Unified Parkinson's Disease Rating Scale part III scores were higher in patients compared to controls (p < 0.001). There was no difference in upper extremity function between patients and controls (right, p = 0.220; left, p = 0.209), but gait was slower in iRBD patients (walking time, p < 0.001; number of steps, p < 0.001). The mean value of the Korean version of the Mini-Mental State Exam and Clinical Dementia Rating were lower in patients (p = 0.006, p = 0.003, respectively). Patients with were also more depressed (p = 0.002), had decreased olfactory function (p < 0.001), reported more frequent sleep/fatigue episodes (p < 0.001), worse attention/memory capacity (p < 0.001), gastrointestinal problems (p = 0.009), urinary problems (p = 0.007), and pain (p = 0.083). Further, iRBD patients reported more frequent sleep-related disturbances (p = 0.004), but no difference in daytime sleepiness (p = 0.663). Disease severity was correlated with pain (r = 0.686, p = 0.002) and visuospatial function (r= -0.507, p = 0.038). There were no correlations between RBD severity and striatal dopaminergic activities (p > 0.09). CONCLUSIONS: iRBD is a multisystem neurodegenerative disorder, and gait abnormalities may be a disease characteristic, possibly related to the akinetic-rigid phenotype of Parkinson's disease. The correlation between pain/visuospatial dysfunction and RBD severity may be related to its pathogenesis.

Diagnostic performance of deep learning models for detecting bone metastasis on whole-body bone scan in prostate cancer.

PURPOSE: We evaluated the performance of deep learning classifiers for bone scans of prostate cancer patients. METHODS: A total of 9113 consecutive bone scans (5342 prostate cancer patients) were initially evaluated. Bone scans were labeled as positive/negative for bone metastasis using clinical reports and image review for ground truth diagnosis. Two different 2D convolutional neural network (CNN) architectures were proposed: (1) whole body-based (WB) and (2) tandem architectures integrating whole body and local patches, here named as "global-local unified emphasis" (GLUE). Both models were trained using abundant (72%:8%:20% for training:validation:test sets) and limited training data (10%:40%:50%). The allocation of test sets was rotated across all images: therefore, fivefold and twofold cross-validation test results were available for abundant and limited settings, respectively. RESULTS: A total of 2991 positive and 6142 negative bone scans were used as input. For the abundant training setting, the receiver operating characteristics curves of both the GLUE and WB models indicated excellent diagnostic ability in terms of the area under the curve (GLUE: 0.936-0.955, WB: 0.933-0.957, P > 0.05 in four of the fivefold tests). The overall accuracies of the GLUE and WB models were 0.900 and 0.889, respectively. With the limited training setting, the GLUE models showed significantly higher AUCs than the WB models (0.894-0.908 vs. 0.870-0.877, P < 0.0001). CONCLUSION: Our 2D-CNN models accurately classified bone scans of prostate cancer patients. While both showed excellent performance with the abundant dataset, the GLUE model showed higher performance than the WB model in the limited data setting.

Diagnostic and prognostic values of 2-[18F]FDG PET/CT in resectable thymic epithelial tumour.

OBJECTIVES: We aimed to evaluate the diagnostic ability for the prediction of histologic grades and prognostic values on recurrence and death of pretreatment 2-[18F]FDG PET/CT in patients with resectable thymic epithelial tumours (TETs). METHODS: One hundred and fourteen patients with TETs who underwent pretreatment 2-[18F]FDG PET/CT between 2012 and 2018 were retrospectively evaluated. TETs were classified into three histologic subtypes: low-risk thymoma (LRT, WHO classification A/AB/B1), high-risk thymoma (HRT, B2/B3), and thymic carcinoma (TC). Area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic performance of PET/CT variables (maximum standardised uptake value [SUVmax], metabolic tumour volume [MTV], total lesion glycolysis [TLG], maximum diameter). Cox proportional hazards models were built using PET/CT and clinical variables. RESULTS: The tumours included 52 LRT, 33 HRT, and 29 TC. SUVmax showed good diagnostic ability for differentiating HRT/TC from LRT (AUC 0.84, 95% confidence interval [CI] 0.76 - 0.92) and excellent ability for differentiating TC from LRT/HRT (AUC 0.94, 95% CI 0.90 - 0.98), with significantly higher values than MTV, TLG, and maximum diameter. With an optimal cut-off value of 6.4, the sensitivity, specificity, and accuracy for differentiating TC from LRT/HRT were 69%, 96%, and 89%, respectively. In the multivariable Cox proportional hazards analyses for freedom-from-recurrence, SUVmax was an independent prognostic factor (p < 0.001), whereas MTV and TLG were not. SUVmax was a significant predictor for overall survival in conjunction with clinical stage and resection margin. CONCLUSION: SUVmax showed excellent diagnostic performance for prediction of TC and significant prognostic value in terms of recurrence and survival. KEY POINTS: • Maximum standardised uptake value (SUVmax) shows excellent performance in the differentiation of thymic carcinoma from low- and high-risk thymoma. • SUVmax is an independent prognostic factor for freedom-from-recurrence in the multivariable Cox proportional hazard model and a significant predictor for overall survival. • 2-[18F]FDG PET/CT can provide a useful diagnostic and prognostic imaging biomarker in conjunction with histologic classification and stage and help choose appropriate management for thymic epithelial tumours.

The clinical feasibility of deep learning-based classification of amyloid PET images in visually equivocal cases.

PURPOSE: Although most deep learning (DL) studies have reported excellent classification accuracy, these studies usually target typical Alzheimer's disease (AD) and normal cognition (NC) for which conventional visual assessment performs well. A clinically relevant issue is the selection of high-risk subjects who need active surveillance among equivocal cases. We validated the clinical feasibility of DL compared with visual rating or quantitative measurement for assessing the diagnosis and prognosis of subjects with equivocal amyloid scans. METHODS: 18F-florbetaben scans of 430 cases (85 NC, 233 mild cognitive impairment, and 112 AD) were assessed through visual rating-based, quantification-based, and DL-based methods. DL was trained using 280 two-dimensional PET images (80%) and tested by randomly assigning the remaining (70 cases, 20%) cases and a clinical validation set of 54 equivocal cases. In the equivocal cases, we assessed the agreement among the visual rating, quantification, and DL and compared the clinical outcome according to each modality-based amyloid status. RESULTS: The visual reading was positive in 175 cases, equivocal in 54 cases, and negative in 201 cases. The composite SUVR cutoff value was 1.32 (AUC 0.99). The subject-level performance of DL using the test set was 100%. Among the 54 equivocal cases, 37 cases were classified as positive (Eq(deep+)) by DL, 40 cases were classified by a second-round visual assessment, and 40 cases were classified by quantification. The DL- and quantification-based classifications showed good agreement (83%, κ = 0.59). The composite SUVRs differed between Eq(deep+) (1.47 [0.13]) and Eq(deep-) (1.29 [0.10]; P < 0.001). DL, but not the visual rating, showed a significant difference in the Mini-Mental Status Examination score change during the follow-up between Eq(deep+) (- 4.21 [0.57]) and Eq(deep-) (- 1.74 [0.76]; P = 0.023) (mean duration, 1.76 years). CONCLUSIONS: In visually equivocal scans, DL was more related to quantification than to visual assessment, and the negative cases selected by DL showed no decline in cognitive outcome. DL is useful for clinical diagnosis and prognosis assessment in subjects with visually equivocal amyloid scans.

Comparison of Amyloid ß and Tau Spread Models in Alzheimer's Disease.

Tau and amyloid ß (Aß), 2 key pathogenic proteins in Alzheimer's disease (AD), reportedly spread throughout the brain as the disease progresses. Models of how these pathogenic proteins spread from affected to unaffected areas had been proposed based on the observation that these proteins could transmit to other regions either through neural fibers (transneuronal spread model) or through extracellular space (local spread model). In this study, we modeled the spread of tau and Aß using a graph theoretical approach based on resting-state functional magnetic resonance imaging. We tested whether these models predict the distribution of tau and Aß in the brains of AD spectrum patients. To assess the models' performance, we calculated spatial correlation between the model-predicted map and the actual map from tau and amyloid positron emission tomography. The transneuronal spread model predicted the distribution of tau and Aß deposition with significantly higher accuracy than the local spread model. Compared with tau, the local spread model also predicted a comparable portion of Aß deposition. These findings provide evidence of transneuronal spread of AD pathogenic proteins in a large-scale brain network and furthermore suggest different contributions of spread models for tau and Aß in AD.

Neural substrates of cognitive reserve in Alzheimer's disease spectrum and normal aging.

The concept of cognitive reserve (CR) originated from discrepancies between the degree of brain pathology and the severity of clinical manifestations. CR has been characterized through CR proxies, such as education and occupation complexity; however, such approaches have inherent limitations. Although several methods have been developed to overcome these limitations, they fail to reflect the entire Alzheimer's disease (AD) pathology. Meanwhile, graph theory analysis, one of most powerful and flexible approaches, have established remarkable network properties of the brain. The functional and structural brain networks are damaged in neurodegenerative diseases. Therefore, network analysis has been applied to clarify the characteristics of the disease or give insight. Here, using multimodal neuroimaging, we propose an intuitive model to estimate CR based on its original definition, and explore the neural substrates of CR from the perspective of networks and functional connectivity. A total of 87 subjects (21 AD, 32 mild cognitive impairment, and 34 normal aging) underwent tau and amyloid PET, 3D T1-weighted MR, and resting-state fMRI. We hypothesized CR as a residual of actual cognitive performance and expected performance to be related to quantitative factors, such as AD pathology, demographics, and a genetic factor. Then, we correlated this marker using education and occupation complexity as conventional CR proxies. We validated this marker by testing whether it would modulate the effect of brain pathology on memory function. To examine the neural substrates associated with CR, we performed graph analysis to investigate the association between the CR marker and network measures at different granularities in total subjects, AD spectrum and normal aging, respectively. The CR marker from our model was well associated with education and occupation complexity. More directly, the CR marker was revealed to modify the relationship between brain pathology and memory function among AD spectrum. The CR marker was correlated with the global efficiency of the entire network, nodal clustering coefficient, and local efficiency of the right middle-temporal pole. In connectivity analysis, one cluster of edges centered on right middle-temporal pole was significantly correlated with the CR marker. In subgroup analysis, the network measures of right middle-temporal pole still correlated with the CR marker among AD spectrum. However, right precentral gyrus was revealed to be associated with the CR marker in normal aging. This study demonstrates that our intuitive model using multimodal neuroimaging and network perspective adequately and comprehensively captures CR. From a network perspective, CR is associated with the capacity to process information efficiently in the brain. The right middle-temporal pole was revealed to be a pivotal neural substrate of CR in AD spectrum. These findings foster understanding of AD and will be useful to help identify individuals with vulnerability or resistance to AD pathology, and characterize patients for intervention or drug trials.

Differences in gray and white matter 18F-THK5351 uptake between behavioral-variant frontotemporal dementia and other dementias.

PURPOSE: We investigated the regional distribution of 18F-THK5351 uptake in gray (GM) and white matter (WM) in patients with behavioral-variant frontotemporal dementia (bvFTD) and compared it with that in patients with Alzheimer's disease (AD) or semantic dementia (SD). METHODS: 18F-THK-5351 positron emission tomography (PET), 18F-florbetaben PET, magnetic resonance imaging, and neuropsychological testing were performed in 103 subjects including 30, 24, 9, and 8 patients with mild cognitive impairment, AD, bvFTD, and SD, respectively, and 32 normal subjects. Standardized uptake value ratios (SUVRs) of 18F-THK-5351 PET images were measured from six GM and WM regions using cerebellar GM as reference. GM and WM SUVRs and WM/GM ratios, the relationship between GM SUVR and WM/GM ratio, and correlation between SUVR and cognitive function were compared. RESULTS: In AD, both parietal GM (p < 0.001) and WM (p < 0.001) SUVRs were higher than in bvFTD. In AD and SD, the WM/GM ratio decreased as the GM SUVR increased, regardless of lobar region. In AD, memory function correlated with parietal GM (ρ = -0.74, p < 0.001) and WM (ρ = -0.53, p < 0.001) SUVR. In SD, language function correlated with temporal GM SUVR (ρ = -0.69, p = 0.006). The frontal WM SUVR was higher in bvFTD than in AD (p = 0.003) or SD (p = 0.017). The frontal WM/GM ratio was higher in bvFTD than in AD (p < 0.001). In bvFTD, the WM/GM ratio increased more prominently than the GM SUVR only in the frontal lobe (R2 = 0.026). In bvFTD, executive function correlated with frontal WM SUVR (ρ = -0.64, p = 0.014). CONCLUSIONS: Frontal WM 18F-THK5351 uptake was higher in bvFTD than in other dementias. The increase in frontal WM uptake was greater than the increase in GM uptake and correlated with executive function. This suggests that frontal lobe WM 18F-THK5351 uptake reflects neuropathological differences between bvFTD and other dementias.

Lack of association between dopamine transporter loss and non-motor symptoms in patients with Parkinson's disease: a detailed PET analysis of 12 striatal subregions.

INTRODUCTION: Patients with Parkinson's disease (PD) present a variety of non-motor symptoms. However, it remains unclear whether dopamine depletion is related to non-motor symptoms, and which non-motor symptoms are significantly dependent on dopaminergic deficit. METHODS: Forty-one patients with PD who underwent positron emission tomography imaging of dopamine transporters (DATs) were recruited for this study. The striatum was divided into 12 subregions, and DAT activity, as striatal dopaminergic concentration, was calculated in each subregion. In addition to measuring motor symptoms using the Unified Parkinson's Disease Rating Scale-part III (UPDRS-III), various non-motor symptoms were assessed using the Montreal cognitive assessment, frontal assessment battery, Beck depression inventory (BDI), Beck anxiety inventory, PD sleep scale (PDSS), PD fatigue scale, and non-motor symptoms scale (NMSS) for PD. RESULTS: For simple linear regression analyses, dopaminergic depletion in all striatal subregions was negatively correlated with the UPDRS-III score. The most relevant non-motor symptom assessment related to dopaminergic loss in the 12 subregions was NMSS, followed by BDI and PDSS. However, following multiple linear regression analyses, dopaminergic depletion in the 12 striatal subregions was not related with any of the non-motor symptoms. Conversely, dopaminergic deficit in the right anterior and posterior putamen was associated with the UPDRS-III score. CONCLUSIONS: Striatal dopaminergic depletion was not significantly correlated with any of the various non-motor symptoms in PD. Our findings suggest that non-dopaminergic systems are significantly implicated in the pathogenesis of non-motor symptoms in patients with PD.

Does smoking impact dopamine neuronal loss in de novo Parkinson disease?

This study analyzed data from dopamine transporter (DAT) positron emission tomographic scans of 282 male patients with de novo Parkinson disease to investigate whether smoking impacts striatal dopamine neuronal degeneration. Mean DAT activity in the posterior (p = 0.016) and ventral putamen (p = 0.028) was higher in 44 current smokers in comparison to 105 ex-smokers and 133 never-smokers. The severity of baseline motor deficits and the longitudinal increases in levodopa-equivalent doses during follow-up were similar among the 3 groups. These results suggest that current smoking, but not past smoking, protects dopamine neuronal degeneration in the sensorimotor striatum with no additional clinical benefits. Ann Neurol 2017;82:850-854.

Early-onset drug-induced parkinsonism after exposure to offenders implies nigrostriatal dopaminergic dysfunction.

OBJECTIVES: The onset of parkinsonism in patients with drug-induced parkinsonism (DIP) exhibits extensive individual variability following exposure to offending drugs. We investigated whether the individual variations in the onset time of parkinsonism reflected the underlying subtle dopaminergic dysfunction in DIP. METHODS: We enrolled 71 patients with DIP who had visually normal striatal dopamine transporter (DAT) availability in 18F-FP-CIT positron emission tomography scans. According to their exposure durations to the offending drugs prior to onset of the parkinsonism, the patients were divided into the early-onset group (duration ≤6 months; n=35) and delayed-onset group (duration >6 months; n=36). We performed the quantitative analysis of the DAT availability in each striatal subregion between the groups. RESULTS: No patients with DIP had DAT availability that was more than 2 SD below the normal mean of DAT availability. Compared with the delayed-onset group, the early-onset DIP group had decreased DAT availability in the striatal subregions including the posterior putamen (p=0.018), anterior putamen (p=0.011), caudate (p=0.035) and ventral striatum (p=0.027). After adjusting for age, sex and cross-cultural smell identification test scores, a multivariate analysis revealed that the DAT availability in the striatal subregions of the patients with DIP was significantly and positively associated with the natural logarithm of the duration of drug exposure. CONCLUSIONS: These results suggest that a short exposure to the offending drugs before the development of parkinsonism would be associated with subtle nigrostriatal dopaminergic dysfunction in patients with DIP.

Effects of dopaminergic depletion and brain atrophy on neuropsychiatric symptoms in de novo Parkinson's disease.

BACKGROUND: Neuropsychiatric symptoms impact the patients' quality of life and caregivers' burdens in Parkinson's disease (PD). We aimed to investigate the effects of striatal dopaminergic depletion and brain atrophy on the neuropsychiatric symptoms of patients with PD. METHODS: Two hundred and seven patients with de novo drug-naïve PD underwent dopamine transporter (DAT) positron emission tomography and brain MRI scanning. In addition, the patients were assessed with caregiver-administered neuropsychiatric inventory (NPI) questionnaires. To evaluate the effects of DAT uptake, subcortical volume and cortical thinning on the patients' neuropsychiatric symptoms, we performed logistic regression and negative binomial regression analyses on the NPI data after controlling for possible confounders. RESULTS: Frontal cortical thinning was associated with the presence of nighttime behaviour and irritability, and the thinning correlated with the severity of the nighttime behaviour. Temporal cortical thinning was associated with the presence of aggression/agitation, and it correlated with the severity of the aggression/agitation. Subcortical atrophy in the accumbens was associated with the presence of disinhibition and correlated with the severity of the disinhibition. Putamen atrophy and insular thinning were independently associated with the presence of apathy, but only insular thinning correlated with the severity of the apathy. Of the predictors, only frontal cortical thinning correlated with the total NPI score. CONCLUSIONS: The results of this study suggested that accumbens atrophy and frontotemporal cortical thinning, especially frontal cortical thinning, independently contributed to neuropsychiatric symptoms in patients with PD, while DAT uptake did not affect the neuropsychiatric symptoms.

Feasibility of dynamic stress 201Tl/rest 99mTc-tetrofosmin single photon emission computed tomography for quantification of myocardial perfusion reserve in patients with stable coronary artery disease.

PURPOSE: We evaluated the feasibility of dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT imaging using a cardiac camera equipped with cadmium-zinc-telluride detectors for the quantification of myocardial perfusion reserve (MPR). METHODS: Subjects with stable known or suspected coronary artery disease (CAD) who had undergone or were scheduled to undergo fractional flow reserve (FFR) measurement were prospectively enrolled. Dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT imaging was performed using a dedicated multiple pinhole SPECT camera with cadmium-zinc-telluride detectors. MPR was derived using Corridor4DM software. RESULTS: A total of 34 subjects were enrolled (25 men and 9 women; mean age 60.4 years). FFR was measured in 65 coronary arteries with intermediate lesions. The average global MPR was 2.58 ± 1.03. Global MPR was associated with the extent of CAD (P = 0.028) and global summed stress score (r = -0.60, P < 0.001). Regional MPR showed a significant correlation with diameter stenosis (r = -0.57, P < 0.001), minimum lumen diameter (r = 0.50, P < 0.001), summed stress score (r = -0.52, P < 0.001) and FFR (r = 0.52, P < 0.001). The area under the receiver operating characteristic curve of MPR for the diagnosis of functionally significant stenosis (FFR ≤0.8) was 0.79 (P < 0.001). The sensitivity and specificity of regional MPR were 67% and 83%, respectively, using a cut-off value of 2.0. CONCLUSION: Dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT imaging and quantification of MPR is feasible in patients with stable CAD. The preliminary results of this study in a small number of patients require confirmation in a larger cohort to determine their implications for bolstering the role of SPECT imaging in the diagnosis and risk prediction of CAD.

Prognostic value of 18 F-FDG PET/CT parameters in patients who undergo salvage treatments for recurrent squamous cell carcinoma of the larynx and hypopharynx.

BACKGROUND: Recurrent laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC) is commonly associated with poor survival outcomes. We evaluated the prognostic role of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) parameters quantitatively measured in patients who underwent salvage treatments for recurrent LHSCC. METHODS: This study involved 100 consecutive LHSCC patients who underwent 18 F-FDG PET/CT for recurrent staging and subsequent salvage treatments. Maximum standardized uptake value (SUVmax ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using 18 F-FDG PET/CT. Cox proportional hazards regression analyses were used to assess the associations between quantitative 18 F-FDG PET/CT parameters and other clinicopathological factors with progression-free survival (PFS) and overall survival (OS). RESULTS: Two-year postsalvage PFS and OS rates were 67.9% and 74.3%, respectively. All 18 F-FDG PET parameters of SUVmax , MTV, and TLG were significantly associated with poor PFS and OS outcomes after salvage treatment (all P < 0.05). Multivariate analyses revealed that recurrence site, MTV (>6.5 mL), and TLG (>17.1 g) were independent variables predictive of PFS. Karnofsky score, SUVmax (>4.0), and TLG (>17.1 g) were the independent prognostic factors for OS. CONCLUSIONS: 18 F-FDG PET/CT can be useful in predicting postsalvage recurrence and survival in patients with recurrent LHSCC.

Pretreatment tumor SUVmax predicts disease-specific and overall survival in patients with head and neck soft tissue sarcoma.

PURPOSE: Head and neck soft tissue sarcoma (HNSTS) is a rare type of tumor with various histological presentations and clinical behaviors. 18F-FDG PET/CT is being increasingly used for staging, grading, and predicting treatment outcomes in various types of human cancers, although this modality has been rarely studied in the survival prediction of HNSTS. Here we examined the prognostic value of tumor metabolic parameters measured using 18F-FDG PET/CT in patients with HNSTS. METHODS: This study included 36 consecutive patients with HNSTS who underwent 18F-FDG PET/CT scanning prior to treatment at our institution. Tumor gross total volume (GTV) was measured from pretreatment contrast-enhanced CT scans, and maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using pretreatment 18F-FDG PET/CT scans. Univariate and multivariate Cox proportional hazard regression analyses were used to identify associations between imaging parameters and disease-specific survival (DSS) or overall survival (OS). RESULTS: Univariate analyses showed that SUVmax, MTV, and TLG, but not GTV, were significantly associated with DSS and OS (all P < 0.05). After controlling for clinicopathological factors, SUVmax, MTV, and TLG were significantly associated with DSS and OS (all P < 0.05). Patients with a tumor SUVmax value of >7.0 experienced an approximately fivefold increase in mortality in terms of DSS and OS relative to those with a tumor SUVmax <7.0. CONCLUSION: Quantitative metabolic measurements on pretreatment 18F-FDG PET/CT can yield values that are significantly predictive of survival after treatment for HNSTS.

Different loss of dopamine transporter according to subtype of multiple system atrophy.

PURPOSE: The aim of this study was to evaluate whether striatal dopamine transporter (DAT) loss as measured by (18)F-fluorinated-N-3-fluoropropyl-2-b-carboxymethoxy-3-b-(4-iodophenyl) nortropane ([(18)F]FP-CIT) PET differs according to the metabolic subtype of multiple system atrophy (MSA) as assessed by [(18)F]FDG PET. METHODS: This retrospective study included 50 patients with clinically diagnosed MSA who underwent [(18)F]FP-CIT and [(18)F]FDG brain PET scans. The PET images were analysed using 12 striatal subregional volume-of-interest templates (bilateral ventral striatum, anterior caudate, posterior caudate, anterior putamen, posterior putamen, and ventral putamen). The patients were classified into three metabolic subtypes according to the [(18)F]FDG PET findings: MSA-Pm (striatal hypometabolism only), MSA-mixedm (both striatal and cerebellar hypometabolism), and MSA-Cm (cerebellar hypometabolism only). The subregional glucose metabolic ratio (MRgluc), subregional DAT binding ratio (BRDAT), and intersubregional ratio (ISRDAT; defined as the BRDAT ratio of one striatal subregion to that of another striatal subregion) were compared according to metabolic subtype. RESULTS: Of the 50 patients, 13 presented with MSA-Pm, 16 presented with MSA-mixedm, and 21 presented with MSA-Cm. The BRDAT of all striatal subregions in the MSA-Pm and MSA-mixedm groups were significantly lower than those in the MSA-Cm group. The posterior putamen/anterior putamen ISRDAT and anterior putamen/ventral striatum ISRDAT in the MSA-Pm and MSA-mixedm groups were significantly lower than those in the MSA-Cm group. CONCLUSION: Patients with MSA-Pm and MSA-mixedm showed more severe DAT loss in the striatum than patients with MSA-Cm. Patients with MSA-Cm had more diffuse DAT loss than patients with MSA-Pm and MSA-mixedm.

Intratumor Textural Heterogeneity on Pretreatment (18)F-FDG PET Images Predicts Response and Survival After Chemoradiotherapy for Hypopharyngeal Cancer.

BACKGROUND: Increasing evidence suggests that intratumor heterogeneity of solid tumors characterized by textural features on 18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) images is associated with response to chemoradiotherapy (CRT) and survival. The current study aimed to determine whether a similar relationship exists in hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: This study investigated 27 patients with HPSCC who underwent cisplatin-based induction chemotherapy followed by definitive CRT underwent pretreatment (18)F-FDG PET/CT. Standardized uptake value (SUV), metabolic tumor volume (MTV), and textural features (coarseness, busyness, complexity, and contrast) of primary tumors were measured. Patients were classified as nonresponders or responders according to the response evaluation criteria in solid tumors. The capacity of each parameter to classify response was assessed using the Mann-Whitney U test. Cox-proportional hazard models were used to identify variables associated with disease-free survival (DFS) and overall survival (OS). RESULTS: Of 70 patients, 58 (83 %) had complete or partial response after CRT. Responders showed lower maximum SUV (P = 0.037), lower MTV (P = 0.039), lower coarseness (P < 0.001), and busyness (P = 0.015) compared with nonresponders. Multivariate analysis showed that high coarseness (P = 0.001, hazard ratio [HR] 5.65; 95 % confidence interval [CI] 2.12-15.07) and busyness (P = 0.045; HR 2.56; 95 % CI 1.02-6.42) were independently associated with poor DFS, and that high coarseness (P = 0.013; HR 2.48; 95 % CI 1.21-5.09) was independently associated with poor OS. CONCLUSION: Abnormal coarseness in baseline (18)F-FDG PET scans may be useful for predicting response and survival after CRT in HPSCC patients.

Prognostic significance of standardized uptake value and metabolic tumour volume on ¹8F-FDG PET/CT in oropharyngeal squamous cell carcinoma.

PURPOSE: Standardized uptake value (SUV) and metabolic tumour volume (MTV) measured by (18)F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers. However, their prognostic significance in oropharyngeal squamous cell carcinoma (OPSCC) has been investigated in only a few studies and with small cohorts. In the present study we evaluated the ability of SUV, MTV, and total lesion glycolysis (TLG) measured on pretreatment (18)F-FDG PET/CT to predict recurrence and survival outcomes in OPSCC. METHODS: The study included 221 patients with OPSCC who underwent pretreatment (18)F-FDG PET/CT imaging and received definitive treatment at our tertiary referral centre. The PET imaging parameters SUVmax, SUVpeak, MTV and TLG were measured in primary tumours with focal (18)F-FDG uptake. Clinical and imaging variables significantly associated with overall survival (OS) and disease-free survival (DFS) were identified by univariate and multivariate analyses using the Cox proportional hazards model. RESULTS: Overall 5-year OS and DFS rates were 72.0 % and 79.5 %, respectively, during a median follow-up of 61 months (range 18 - 122 months). The cut-off values of tumour SUVmax, SUVpeak, MTV and TLG for prediction of DFS were 7.55, 6.80, 11.06 mL and 78.56 g, respectively. Univariate analyses showed that age >60 years, advanced tumour stage, and high tumour SUVmax, SUVpeak, MTV and TLG were significantly associated with decreased OS and DFS (P < 0.05 each). Age, tumour SUVmax and MTV remained independent variables for OS and DFS (P < 0.05 each) in the multivariate analyses. CONCLUSION: SUVmax and MTV measured on pretreatment (18)F-FDG PET/CT may be useful in predicting the clinical outcomes in OPSCC patients. This study investigated the clinical prognostic value of imaging parameters from pretreatment (18)F-FDG PET/CT in 221 patients who underwent definitive treatment for oropharyngeal squamous cell carcinoma. High maximum standardized uptake value and metabolic tumour volume were independently associated with decreased disease-free and overall survival outcomes.

Preserved Hippocampal Glucose Metabolism on 18F-FDG PET after Transplantation of Human Umbilical Cord Blood-derived Mesenchymal Stem Cells in Chronic Epileptic Rats.

Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) may be a promising modality for treating medial temporal lobe epilepsy. (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a noninvasive method for monitoring in vivo glucose metabolism. We evaluated the efficacy of hUCB-MSCs transplantation in chronic epileptic rats using FDG-PET. Rats with recurrent seizures were randomly assigned into three groups: the stem cell treatment (SCT) group received hUCB-MSCs transplantation into the right hippocampus, the sham control (ShC) group received same procedure with saline, and the positive control (PC) group consisted of treatment-negative epileptic rats. Normal rats received hUCB-MSCs transplantation acted as the negative control (NC). FDG-PET was performed at pre-treatment baseline and 1- and 8-week posttreatment. Hippocampal volume was evaluated and histological examination was done. In the SCT group, bilateral hippocampi at 8-week after transplantation showed significantly higher glucose metabolism (0.990 ± 0.032) than the ShC (0.873 ± 0.087; P < 0.001) and PC groups (0.858 ± 0.093; P < 0.001). Histological examination resulted that the transplanted hUCB-MSCs survived in the ipsilateral hippocampus and migrated to the contralateral hippocampus but did not differentiate. In spite of successful engraftment, seizure frequency among the groups was not significantly different. Transplanted hUCB-MSCs can engraft and migrate, thereby partially restoring bilateral hippocampal glucose metabolism. The results suggest encouraging effect of hUCB-MSCs on restoring epileptic networks.