Molecular Imaging of P-glycoprotein in Chemoresistant Tumors Using a Dual-Modality PET/Fluorescence Probe.

Overexpression of P-glycoprotein (Pgp) has been considered a primary cause for multidrug resistance in a variety of cancers for three decades. However, clinical translation of Pgp targeted therapeutics has been hindered by lack of patient preselection based on the Pgp presence in tumors. We aim to develop a molecularly targeted probe for imaging tumoral Pgp in vivo with positron emission tomography (PET) and fluorescence, and to provide a tool for preselecting the patients with tumoral Pgp expression. Thus, a Pgp monoclonal antibody 15D3 was chemically modified with IRDye800 (IR800) and DOTA chelator. The specificity of the antibody conjugates DOTA-Pab-IR800 was verified in Pgp-expressing 3T3-MDR1 and control 3T3 cells. After radiolabeling with 64Cu, the probe was applied in small animal PET imaging of Pgp in a mouse xenograft model of NCI/ADR-Res cells, which are chemoresistant through overexpression of Pgp. Quantification analysis of the PET images demonstrated that the tumor uptake of the radioactive probe was 9.9 ± 1.4, 12.1 ± 1.2, and 10.5 ± 1.0%ID/g at 4, 24, and 48 h post injection. The tumor-to-muscle ratio was 20.9 at 48 h post injection based on biodistribution studies. Fluorescence imaging was performed following PET experiments, and it demonstrated excellent tumor accumulation of this dual-modality probe in the NCI/ADR-Res tumors. Further, an image-guided surgery was successfully performed using the fluorescence modality of the probe, demonstrating potential utility of this probe in image-guided surgical removal of Pgp-positive drug resistant tumors in the patients. In conclusion, this study clearly demonstrated that the Pgp-targeted antibody probe, 64Cu-DOTA-Pab-IR800, could provide a promising diagnosis tool for detection of Pgp-expressing tumors in vivo.

Comparison of RECIST, EORTC criteria and PERCIST for evaluation of early response to chemotherapy in patients with non-small-cell lung cancer.

PURPOSE: To compare the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the European Organization for Research and Treatment of Cancer (EORTC) criteria and the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0 using PET volume computer-assisted reading (PET VCAR) for response evaluation in patients with advanced non-small-cell lung cancer (NSCLC) treated with chemotherapy. METHODS: A total of 35 patients with NSCLC were included in this prospective study. All patients received standard chemotherapy and underwent (18)F-FDG PET/CT scans before and after treatment. With the assistance of PET VCAR, the chemotherapeutic responses were evaluated according to the RECIST 1.1, EORTC criteria and PERCIST 1.0. Concordance among these protocols was assessed using Cohen's κ coefficient and Wilcoxon's signed-ranks test. Progression-free survival (PFS) was calculated using the Kaplan-Meier test. RESULTS: RECIST 1.1 and EORTC response classifications were discordant in 20 patients (57.1 %; κ = 0.194, P < 0.05), and RECIST 1.1 and PERCIST 1.0 classifications were discordant in 22 patients (62.9 %; κ = 0.139, P < 0.05). EORTC and PERCIST 1.0 classifications were discordant in only 4 patients (11.4 %), resulting in better concordance (κ = 0.804, P > 0.05). Patients with a partial remission according to RECIST 1.1 had significantly longer PFS (P < 0.001) than patients with progressive disease, but not significantly longer than patients with stable disease (P = 0.855). According to both the EORTC criteria and PERCIST 1.0, patients with a partial metabolic response had a significantly longer PFS than those with stable metabolic disease and those with progressive metabolic disease (P = 0.020 and P < 0.001, respectively, for EORTC; both P < 0.001 for PERCIST 1.0). CONCLUSION: EORTC criteria and PERCIST 1.0 are more sensitive and accurate than RECIST 1.1 for the detection of an early therapeutic response to chemotherapy in patients with NSCLC. Although EORTC criteria and PERCIST 1.0 showed similar results, PERCIST 1.0 is preferred because detailed and unambiguous definitions are given. We also found that response evaluations with PERCIST 1.0 using a single lesion and multiple lesions gave similar response classifications.

[Evaluation of white matter myelination in preterm infants using DTI and MRI].

OBJECTIVE: To investigate the features of white matter myelin development in preterm infants using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). METHODS: A total of 31 preterm infants with a gestational age of ≤32 weeks and a birth weight of <1 500 g were enrolled. According to head MRI findings, these infants were divided into preterm group with brain injury (12 infants) and preterm group without brain injury (19 infants). A total of 24 full-term infants were enrolled as control group. Head MRI and DTI were performed at a gestational age or corrected gestational age of 37-40 weeks. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured for the same regions of interest in the three groups. RESULTS: The preterm group with brain injury showed a significantly lower FA value of the posterior limb of the internal capsule than the preterm group without brain injury and full-term control group (P<0.05). The preterm groups with and without brain injury showed significantly lower FA values of frontal white matter and lenticular nucleus than the full-term control group (P<0.05). The FA value of occipital white matter showed no significant differences among the three groups (P>0.05). Compared with the full-term control group, the preterm groups with and without brain injury showed significantly higher ADC values of the posterior limb of the internal capsule, lenticular nucleus, occipital white matter, and frontal white matter (P<0.05). CONCLUSIONS: After brain injury, preterm infants tend to develop disorder or delay of white matter myelination in the posterior limb of the internal capsule. At a corrected full-term gestational age, the preterm infants with and without brain injury have a lower grade of maturity in periventricular white matter and grey matter than full-term infants.

Alterations of apparent diffusion coefficient from ultra high b-values in the bilateral thalamus and striatum in MRI-negative drug-resistant epilepsy.

OBJECTIVE: Subcortical nuclei such as the thalamus and striatum have been shown to be related to seizure modulation and termination, especially in drug-resistant epilepsy. Enhance diffusion-weighted imaging (eDWI) technique and tri-component model have been used in previous studies to calculate apparent diffusion coefficient from ultra high b-values (ADCuh). This study aimed to explore the alterations of ADCuh in the bilateral thalamus and striatum in MRI-negative drug-resistant epilepsy. METHODS: Twenty-nine patients with MRI-negative drug-resistant epilepsy and 18 healthy controls underwent eDWI scan with 15 b-values (0-5000 s/mm2). The eDWI parameters including standard ADC (ADCst), pure water diffusion (D), and ADCuh were calculated from the 15 b-values. Regions-of-interest (ROIs) analyses were conducted in the bilateral thalamus, caudate nucleus, putamen, and globus pallidus. ADCst, D, and ADCuh values were compared between the MRI-negative drug-resistant epilepsy patients and controls using multivariate generalized linear models. Inter-rater reliability was assessed using the intra-class correlation coefficient (ICC) and Bland-Altman (BA) analysis. False discovery rate (FDR) method was applied for multiple comparisons correction. RESULTS: ADCuh values in the bilateral thalamus, caudate nucleus, putamen, and globus pallidus in MRI-negative drug-resistant epilepsy were significantly higher than those in the healthy control subjects (all p < 0.05, FDR corrected). SIGNIFICANCE: The alterations of the ADCuh values in the bilateral thalamus and striatum in MRI-negative drug-resistant epilepsy might reflect abnormal membrane water permeability in MRI-negative drug-resistant epilepsy. ADCuh might be a sensitive measurement for evaluating subcortical nuclei-related brain damage in epilepsy patients. PLAIN LANGUAGE SUMMARY: This study aimed to explore the alterations of apparent diffusion coefficient calculated from ultra high b-values (ADCuh) in the subcortical nuclei such as the bilateral thalamus and striatum in MRI-negative drug-resistant epilepsy. The bilateral thalamus and striatum showed higher ADCuh in epilepsy patients than healthy controls. These findings may add new evidences of subcortical nuclei abnormalities related to water and ion hemostasis in epilepsy patients, which might help to elucidate the underlying epileptic neuropathophysiological mechanisms and facilitate the exploration of therapeutic targets.

A PET-based radiomics nomogram for individualized predictions of seizure outcomes after temporal lobe epilepsy surgery.

PURPOSE: To establish and validate a novel nomogram based on clinical characteristics and [18F]FDG PET radiomics for the prediction of postsurgical seizure freedom in patients with temporal lobe epilepsy (TLE). PATIENTS AND METHODS: 234 patients with drug-refractory TLE patients were included with a median follow-up time of 24 months after surgery. The correlation coefficient redundancy analysis and LASSO Cox regression were used to characterize risk factors. The Cox model was conducted to develop a Clinic-PET nomogram to predict the relapse status in the training set (n = 171). The nomogram's performance was estimated through discrimination, calibration, and clinical utility. The prognostic prediction model was validated in the test set (n = 63). RESULTS: Eight radiomics features were selected to assess the radiomics score (radscore) of the operation side (Lat_radscore) and the asymmetric index (AI) of the radiomics score (AI_radscore). AI_radscor, Lat_radscor, secondarily generalized seizures (SGS), and duration between seizure onset and surgery (Durmon) were significant predictors of seizure-free outcomes. The final model had a C-index of 0.68 (95 %CI: 0.59-0.77) for complete freedom from seizures and time-dependent AUROC was 0.65 at 12 months, 0.65 at 36 months, and 0.59 at 60 months in the test set. A web application derived from the primary predictive model was displayed for economic and efficient use. CONCLUSIONS: A PET-based radiomics nomogram is clinically promising for predicting seizure outcomes after temporal lobe epilepsy surgery.

Prospective evaluation of term neonate brain damage following preceding hypoxic sentinel events using enhanced T2* weighted angiography (eSWAN).

PURPOSE: To evaluate the brain damage of term neonates with evidence of a preceding hypoxic sentinel event using eSWAN prospectively. METHODS: The study was approved by the institutional research ethics committee. Among the neonates who were examined during the first 8 days after birth with conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI) and eSWAN, 39 neonates with a preceding acute hypoxic sentinel event were divided into two groups: the hypoxic ischaemic encephalopathy (HIE) group and the high-risk group. Twenty-five neonates were normal control subjects. Conventional MRI, DWI, and T2* and R2* maps from eSWAN were assessed. T2* and R2* values from T2* and R2* maps were calculated in predefined regions in the HIE and high-risk groups and then compared with those in control subjects. RESULTS: The neonates in the HIE and high-risk groups showed a high percentage of cerebral oedema and periventricular white-matter (PWM) lesions. Cerebral oedema and haemorrhagic lesions of PWM were more highly visible on the T2* map compared with conventional MRI: cerebral oedema was illustrated as a high T2* area and haemorrhagic lesions had a significantly lower T2* on the T2* map. Lower R2* values of lentiform nuclei (LN) and a higher T2* and lower R2* of frontal white matter (FWM) were found in neonates in the HIE group relative to those of normal controls. The T2* value of LN in the high-risk group was higher than that of the normal controls. CONCLUSIONS: The T2* map from eSWAN is useful in detecting cerebral oedema and haemorrhagic lesions of PWM in neonates. The measurement of T2* and R2* values is helpful in assessing the LN and FWM damage in neonates following a hypoxic sentinel event.

Comparison of 18 F-FDOPA and 18 F-MFBG PET/CT Images of Metastatic Pheochromocytoma.

ABSTRACT: A 30-year-old man with pheochromocytoma was hospitalized for hemoptysis without inducement. CT revealed a mass in the left lung, and biopsy pathology under the bronchoscope suggested that it was a pheochromocytoma metastasis. To further identify the location of the metastatic lesions, the patient was enrolled in a clinical trial and underwent 18 F-FDOPA and 18 F-MFBG PET/CT. Images from both examinations showed similar lesions. However, the lesions differed in that the uptake of some lesions was significantly higher with 18 F-FDOPA than with 18 F-MFBG, whereas the para-aortic lesion was active in 18 F-MFBG but not in 18 F-FDOPA.

Precision of quantitative parameters of 18F-FDG PET/CT in a rabbit VX2 tumor model.

Background: The precision reflecting repeated measurement error of quantitative parameters of flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for evaluating the therapeutic effect of solid tumor can help observe whether a real biologic change in glucose metabolism occurred, or if the change was caused by errors before and after the treatment. Methods: A total of 18 VX2 tumor-bearing male New Zealand rabbits confirmed by pathology were used, three of which were used for determining the best scanning time point after injection and 15 for a precision experiment by repeating PET/CT scans for three consecutive days. The PET volume computer-assisted reading (PET VCAR) software (GE Healthcare) was used to analyze the standardized uptake value (SUV) and total lesion glycolysis (TLG) parameters. The lean body mass (LBM) to calculate the SUV corrected for lean body mass (SUL) parameters was measured using dual energy X-ray absorptiometry (DXA). The precision was represented as the coefficient of variation of root mean square (RMS-CV) and standard deviation of root mean square (RMS-SD). The least significant change (LSC) was also calculated when considering precision. Results: The precision of SUV parameters, including SUVmax, SUVmean and SUVpeak ranged from 18.3% to 18.8%, which was similar to that of the SUL parameters (18.0-18.4%). Using 80% confidence interval (CI), the LSC of SUVmax and SULpeak were 33.1% and 33.3%, respectively; using 95% CI, the LSC of SUVmax and SULpeak were 50.1% and 51.0%, respectively. Conclusions: This research established the method of precision in a rabbit VX2 tumor model, which can be used for monitoring changes to assess the effects of drug treatment on solid tumors in experimental studies with 18F-FDG PET/CT imaging.

Predictive value of metabolic parameters derived from preoperative 18F-FDG positron emission tomography/computed tomography for brain metastases in patients with surgically resected non-small cell lung cancer.

Background: Brain metastases (BMs) are common complications in patients with non-small cell lung cancer (NSCLC). The purpose of this study was to investigate whether the metabolic parameters derived from preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) can predict BM development in patients with surgically resected NSCLC. Methods: We retrospectively reviewed 128 consecutive patients with stage I-IIIA NSCLC who underwent 18F-FDG PET/CT before curative surgery at The First Affiliated Hospital of Jinan University between November 2012 and October 2021. By drawing a volume of interest (VOI), the maximum standardized uptake values (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor as well as the mean SUV (SUVmean) of the liver and arterial blood were measured. The tumor-to-liver SUV ratio (TLR) and tumor-to-blood SUV ratio (TBR) were also calculated. Receiver operating characteristic curve analysis was used to determine the best cut-off values for positron emission tomography (PET) parameters to predict BM-free survival, and Cox proportional hazards regression analysis was used to assess the predictive value of clinical variables and PET parameters. Results: The median follow-up duration for survival patients was 23.4 months, and 15 patients (11.7%) experienced BM as the initial relapse site. The cumulative rates of BM over the course of 1, 2, and 5 years were 4.5%, 10.5%, and 17.5%, respectively. The optimal cut-off values for the prediction of BM-free survival were 7.7, 4.9, and 4.5 for SUVmax, TLR, and TBR, and 5.5 mL and 16.1 for MTV and TLG, respectively. In the Cox proportional hazards model, the risk of BM was significantly associated with TLR [hazard ratio (HR) =10.712; 95% confidence interval (CI): 2.958-38.801; P<0.001] and MTV (HR =3.150; 95% CI: 0.964-10.293; P=0.020) after adjusting for tumor stage, clinicopathological factors, and other PET parameters. Conclusions: Preoperative TLR and MTV of the primary tumor may be helpful in predicting BM development in patients with surgically resected NSCLC. Tumor metabolic parameters may potentially be used to stratify the risk of BM and determine individualized surveillance strategies.

18F-FDG PET/CT and PET/MRI fusion imaging for neuroendocrine carcinoma of the tongue: A case report.

Neuroendocrine carcinoma (NEC) involving the tongue is a rare and aggressive disease that is more common in middle-aged and elderly males. We report a case of a 56-year-old male who presented to our hospital with sore throat and was found to have a mass in the left root of the tongue. 18F-FDG PET/CT revealed intense FDG uptake in the mass of the tongue base, as well as different uptake of FDG in the mid-posterior mediastinal mass, right adrenal gland, and enlarged lymph nodes in the neck and mediastinum. Gadolinium-enhanced MRI clearly showed the extent of the tongue lesion, additionally suggesting the presence of brain metastases. 18F-FDG PET/MRI fusion images of the neck were obtained on the workstation, which may have a higher diagnostic value for tongue NEC. The patient underwent a biopsy of the mass in the left root of the tongue and was pathologically diagnosed with NEC. Whole-body 18F-FDG PET/CT and regional PET/MRI fusion images have complementary roles in the diagnosis of tongue NEC, and the former is mainly applied to determine the clinical stage of the disease and to guide treatment.

Predictive value of baseline metabolic tumor burden on 18F-FDG PET/CT for brain metastases in patients with locally advanced non-small-cell lung cancer.

Objectives: Brain metastases (BMs) are a major cause leading to the failure of treatment management for non-small-cell lung cancer (NSCLC) patients. The purpose of this study was to evaluate the predictive value of baseline metabolic tumor burden on 18F-FDG PET/CT measured with metabolic tumor volume (MTV) and total lesion glycolysis (TLG) for brain metastases (BMs) development in patients with locally advanced non-small-cell lung cancer (NSCLC) after treatment. Methods: Forty-seven patients with stage IIB-IIIC NSCLC who underwent baseline 18F-FDG PET/CT examinations were retrospectively reviewed. The maximum standardized uptake value (SUVmax), MTV, and TLG of the primary tumor (SUVmaxT, MTVT, and TLGT), metastatic lymph nodes (SUVmaxN, MTVN, and TLGN), and whole-body tumors (SUVmaxWB, MTVWB, and TLGWB) were measured. The optimal cut-off values of PET parameters to predict brain metastasis-free survival were obtained using Receiver operating characteristic (ROC) analysis, and the predictive value of clinical variables and PET parameters were evaluated using Cox proportional hazards regression analysis. Results: The median follow-up duration was 25.0 months for surviving patients, and 13 patients (27.7%) developed BM. The optimal cut-off values were 21.1 mL and 150.0 g for MTVT and TLGT, 20.0, 10.9 mL and 55.6 g for SUVmaxN, MTVN and TLGN, and 27.9, 27.4 mL and 161.0 g for SUVmaxWB, MTVWB and TLGWB, respectively. In the Cox proportional hazards models, the risk of BM was significantly associated with MTVN and MTVWB or TLGN and TLGWB after adjusting for histological cell type, N stage, SUVmaxN, and SUVmaxWB. Conclusions: Baseline metabolic tumor burden (MTV and TLG) evaluated from the level of metastatic lymph nodes and whole-body tumors are significant predictive factors for BM development in patients with locally advanced NSCLC.

Positron Emission Tomography in the Neuroimaging of Autism Spectrum Disorder: A Review.

Autism spectrum disorder (ASD) is a basket term for neurodevelopmental disorders characterized by marked impairments in social interactions, repetitive and stereotypical behaviors, and restricted interests and activities. Subtypes include (A) disorders with known genetic abnormalities including fragile X syndrome, Rett syndrome, and tuberous sclerosis and (B) idiopathic ASD, conditions with unknown etiologies. Positron emission tomography (PET) is a molecular imaging technology that can be utilized in vivo for dynamic and quantitative research, and is a valuable tool for exploring pathophysiological mechanisms, evaluating therapeutic efficacy, and accelerating drug development in ASD. Recently, several imaging studies on ASD have been published and physiological changes during ASD progression was disclosed by PET. This paper reviews the specific radioligands for PET imaging of critical biomarkers in ASD, and summarizes and discusses the similar and different discoveries in outcomes of previous studies. It is of great importance to identify general physiological changes in cerebral glucose metabolism, cerebral blood flow perfusion, abnormalities in neurotransmitter systems, and inflammation in the central nervous system in ASD, which may provide excellent points for further ASD research.

The precision study of dual energy X-ray absorptiometry for bone mineral density and body composition measurements in female cynomolgus monkeys.

Background: Dual-energy X-ray absorptiometry (DXA) is a well-accepted tool for monitoring skeletal and body composition changes in biomedical studies. The nonhuman primate model is suitable for studies exploring the pathogenesis of and novel treatments for osteoporosis. Our objectives are to determine the precision of DXA detection in cynomolgus monkeys and to identify the difference in precision in lumbar bone mineral density (BMD) with various segment selections. Methods: Thirty adult female cynomolgus monkeys underwent duplicate total body DXA scans. Total body bone mineral density (BMDTB) and body composition, including bone mineral content (BMCTB), lean mass (LMTB), and fat mass (FMTB), were analyzed by enCORE software, while lumbar BMD was obtained by manual region-of-interest analysis. The precision was represented as the root-mean-square standard deviation (RMS-SD) and coefficient of variation (RMS-CV%), and least significant changes (LSCs) were reported. Results: The RMS-SD (RMS-CV%) of the repeated DXA analyses for BMDTB, BMCTB, LMTB and FMTB were 0.002 g/cm2 (0.50%), 0.90 g (0.42%), 0.015 kg (0.49%), and 0.031 kg (2.71%), respectively. The regional BMD precision (RMS-CV%) of the lumbar spine with various combinations ranged from 0.70% to 1.09%, The LSCs with 80% statistical confidence (LSC80) ranged from 1.27% to 1.97%, and LSC95 ranged from 1.94% to 3.01%. Conclusions: DXA provided excellent reproducibility in the measurements of BMD and body composition in nonhuman primates. We find DXA reliable for total and regional measurement in skeletal research and the evaluation of osteoporosis treatment with monkeys as animal models.

Analysis of serum bone turnover markers in female cynomolgus monkeys of different ages.

Objective: The purpose of this study was to examine bone turnover markers, estradiol, parathyroid hormone, and 25 hydroxyvitamin D, in cynomolgus monkeys at different ages to improve our understanding of the changes in bone turnover markers throughout the life cycle of cynomolgus monkeys and to provide a basis for the establishment of a non-human primate model of osteoporosis. Methods: Total Body Bone Mineral Density and Total Body Bone Mineral Content were measured using Dual-Energy X-Ray Absorptiometry in cynomolgus monkeys at different ages. Serum bone turnover marker' levels were measured using enzyme immunoassays at each age group, and the relationship between bone turnover markers and age was assessed by Spearman rank correlation analysis to investigate the relationship between bone turnover markers and age in female cynomolgus monkeys. Results: Total Body Bone Mineral Density in female cynomolgus monkeys peaked at 10 years of age and then formed a plateau that was maintained until old age. Procollagen I Aminoterminal Propeptide, Bone Alkaline Phosphatase, Osteocalcin, and C-Terminal Telopeptide Of Type I Collagen peaked at 1 to 3 years of age and gradually decreased with age, leveling off by 10 years of age. Estradiol, parathyroid hormone, and 25 hydroxyvitamin D, follicle-stimulating hormone, luteinizing hormone, were not significantly different among age groups. Conclusion: This paper provides data on trends in bone turnover markers throughout the life cycle of female cynomolgus monkeys, which are similar to human changes.

Early detection of secondary damage in ipsilateral thalamus after acute infarction at unilateral corona radiata by diffusion tensor imaging and magnetic resonance spectroscopy.

BACKGROUND: Traditional magnetic resonance (MR) imaging can identify abnormal changes in ipsilateral thalamus in patients with unilateral middle cerebral artery (MCA) infarcts. However, it is difficult to demonstrate these early changes quantitatively. Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (MRS) are potentially sensitive and quantitative methods of detection in examining changes of tissue microstructure and metabolism. In this study, We used both DTI and MRS to examine possible secondary damage of thalamus in patients with corona radiata infarction. METHODS: Twelve patients with unilateral corona radiata infarction underwent MR imaging including DTI and MRS at one week (W1), four weeks (W4), and twelve weeks (W12) after onset of stroke. Twelve age-matched controls were imaged. Mean diffusivity (MD), fractional anisotropy (FA), N-acetylaspartate (NAA), choline(Cho), and creatine(Cr) were measured in thalami. RESULTS: T1-weighted fluid attenuation inversion recovery (FLAIR), T2-weighted, and T2-FLAIR imaging showed an infarct at unilateral corona radiate but no other lesion in each patient brain. In patients, MD was significantly increased at W12, compared to W1 and W4 (all P< 0.05). NAA was significantly decreased at W4 compared to W1, and at W12 compared to W4 (all P< 0.05) in the ipsilateral thalamus. There was no significant change in FA, Cho, or Cr in the ipsilateral thalamus from W1 to W12. Spearman's rank correlation analysis revealed a significant negative correlation between MD and the peak area of NAA, Cho, and Cr at W1, W4, and W12 and a significant positive correlation of FA with NAA at W1. CONCLUSIONS: These findings indicate that DTI and MRS can detect the early changes indicating secondary damage in the ipsilateral thalamus after unilateral corona radiata infarction. MRS may reveal the progressive course of damage in the ipsilateral thalamus over time.

A method for evaluation of patient-specific lean body mass from limited-coverage CT images and its application in PERCIST: comparison with predictive equation.

BACKGROUND: Standardized uptake value (SUV) normalized by lean body mass ([LBM] SUL) is recommended as metric by PERCIST 1.0. The James predictive equation (PE) is a frequently used formula for LBM estimation, but may cause substantial error for an individual. The purpose of this study was to introduce a novel and reliable method for estimating LBM by limited-coverage (LC) CT images from PET/CT examinations and test its validity, then to analyse whether SUV normalised by LC-based LBM could change the PERCIST 1.0 response classifications, based on LBM estimated by the James PE. METHODS: First, 199 patients who received whole-body PET/CT examinations were retrospectively retrieved. A patient-specific LBM equation was developed based on the relationship between LC fat volumes (FVLC) and whole-body fat mass (FMWB). This equation was cross-validated with an independent sample of 97 patients who also received whole-body PET/CT examinations. Its results were compared with the measurement of LBM from whole-body CT (reference standard) and the results of the James PE. Then, 241 patients with solid tumours who underwent PET/CT examinations before and after treatment were retrospectively retrieved. The treatment responses were evaluated according to the PE-based and LC-based PERCIST 1.0. Concordance between them was assessed using Cohen's κ coefficient and Wilcoxon's signed-ranks test. The impact of differing LBM algorithms on PERCIST 1.0 classification was evaluated. RESULTS: The FVLC were significantly correlated with the FMWB (r=0.977). Furthermore, the results of LBM measurement evaluated with LC images were much closer to the reference standard than those obtained by the James PE. The PE-based and LC-based PERCIST 1.0 classifications were discordant in 27 patients (11.2%; κ = 0.823, P=0.837). These discordant patients' percentage changes of peak SUL (SULpeak) were all in the interval above or below 10% from the threshold (±30%), accounting for 43.5% (27/62) of total patients in this region. The degree of variability is related to changes in LBM before and after treatment. CONCLUSIONS: LBM algorithm-dependent variability in PERCIST 1.0 classification is a notable issue. SUV normalised by LC-based LBM could change PERCIST 1.0 response classifications based on LBM estimated by the James PE, especially for patients with a percentage variation of SULpeak close to the threshold.

Localizing Epileptic Foci Before Surgery in Patients With MRI-Negative Refractory Epilepsy Using Statistical Parameter Mapping and Three-Dimensional Stereotactic Surface Projection Based on 18F-FDG PET.

Patients with refractory epilepsy are not only free of seizures after resecting epileptic foci, but also experience significantly improved quality of life. Fluorine-18-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) is a promising avenue for detecting epileptic foci in patients with magnetic resonance imaging (MRI)-negative refractory epilepsy. However, the detection of epileptic foci by visual assessment based on 18F-FDG PET is often complicated by a variety of factors in clinical practice. Easy imaging methods based on 18F-FDG PET images, such as statistical parameter mapping (SPM) and three-dimensional stereotactic surface projection (3D-SSP), can objectively detect epileptic foci. In this study, the regions of surgical resection of patients with over 1 year follow-up and no seizures were defined as standard epileptic foci. We retrospectively analyzed the sensitivity of visual assessment, SPM and 3D-SSP based on 18F-FDG PET to detect epileptic foci in MRI-negative refractory epilepsy patients and obtained the sensitivities of visual assessment, SPM and 3D-SSP are 57, 70 and 60% respectively. Visual assessment combined with SPM or 3D-SSP can improve the sensitivity of detecting epileptic foci. The sensitivity was highest when the three methods were combined, but decreased consistency, in localizing epileptic foci. We conclude that SPM and 3D-SSP can be used as objective methods to detect epileptic foci before surgery in patients with MRI-negative refractory epilepsy. Visual assessment is the preferred method for PET image analysis in MRI-negative refractory epilepsy. When the visual assessment is inconsistent with the patient's electroclinical information, SPM or 3D-SSP was further selected to assess the epileptic foci. If the combination of the two methods still fails to accurately locate the epileptic foci, comprehensive evaluation can be performed by combining the three methods.

Electroclinical and Multimodality Neuroimaging Characteristics and Predictors of Post-Surgical Outcome in Focal Cortical Dysplasia Type IIIa.

Focal cortical dysplasia (FCD) type IIIa is an easily ignored cause of intractable temporal lobe epilepsy. This study aimed to analyze the clinical, electrophysiological, and imaging characteristics in FCD type IIIa and to search for predictors associated with postoperative outcome in order to identify potential candidates for epilepsy surgery. We performed a retrospective review including sixty-six patients with FCD type IIIa who underwent resection for drug-resistant epilepsy. We evaluated the clinical, electrophysiological, and neuroimaging features for potential association with seizure outcome. Univariate and multivariate analyses were conducted to explore their predictive role on the seizure outcome. We demonstrated that thirty-nine (59.1%) patients had seizure freedom outcomes (Engel class Ia) with a median postsurgical follow-up lasting 29.5 months. By univariate analysis, duration of epilepsy (less than 12 years) (p = 0.044), absence of contralateral insular lobe hypometabolism on PET/MRI (p Log-rank = 0.025), and complete resection of epileptogenic area (p Log-rank = 0.004) were associated with seizure outcome. The incomplete resection of the epileptogenic area (hazard ratio = 2.977, 95% CI 1.218-7.277, p = 0.017) was the only independent predictor for seizure recurrence after surgery by multivariate analysis. The results of past history, semiology, electrophysiological, and MRI were not associated with seizure outcomes. Carefully included patients with FCD type IIIa through a comprehensive evaluation of their clinical, electrophysiological, and neuroimaging characteristics can be good candidates for resection. Several preoperative factors appear to be predictive of the postoperative outcome and may help in optimizing the selection of ideal candidates to benefit from epilepsy surgery.

Sequential PET/diffusion-weighted imaging in the evaluation of myocardial perfusion and viability in coronary artery disease: a preliminary study.

OBJECTIVES: To evaluate the utility of sequential F-18 fluorodeoxyglucose PET/diffusion-weighted imaging in assessing myocardial perfusion and viability in coronary artery disease. METHODS: Fourteen coronary artery disease patients and five non-coronary artery disease subjects underwent sequential cardiac F-18 fluorodeoxyglucose PET/diffusion-weighted imaging using a trimodality PET/computed tomography-MRI system. The perfusion data were acquired by measuring low b-values apparent diffusion coefficient using diffusion-weighted imaging. Regional myocardial viability was determined by perfusion/metabolism patterns. The perfusion/metabolism patterns obtained by low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake were analyzed and compared with the results from the combination of rest methoxyisobutylisonitrile (Tc-MIBI) myocardial perfusion single-photon emission computed tomography with F-18 fluorodeoxyglucose PET/computed tomography. RESULTS: Ten coronary artery disease patients and five non-coronary artery disease subjects were included in the final analysis. Low b-values apparent diffusion coefficient defects involved with 25 myocardial regions were demonstrated in nine coronary artery disease patients, while Tc-MIBI defects involved with 21 myocardial regions were shown in the same patients. The agreement between low b-values apparent diffusion coefficient and MIBI uptake was good in coronary artery disease patients (κ = 0.627, P < 0.001) and was better still in the whole subjects (κ = 0.733, P < 0.001). Low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake demonstrated mismatch patterns in six coronary artery disease patients and MIBI/fluorodeoxyglucose uptake revealed mismatch patterns in seven coronary artery disease patients. Agreement in the evaluation of regional myocardial viability between low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake and MIBI/fluorodeoxyglucose uptake was high in coronary artery disease patients (κ = 0.627, P < 0.001) and all subjects (κ = 0.728, P < 0.001). CONCLUSIONS: Low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake is comparable to MIBI/fluorodeoxyglucose uptake in assessing perfusion/metabolism patterns, indicating that microperfusion might dominate the diffusion signal at low b-values and sequential PET/diffusion-weighted imaging might be useful to evaluate myocardial viability in coronary artery disease patients.

Preliminary clinical results for PET/MR compared with PET/CT in patients with nasopharyngeal carcinoma.

The present study aimed to assess the performance of positron emission tomography­magnetic resonance imaging (PET/MR) for the visualization and characterization of lesions. In addition, the present study investigated whether the apparent diffusion coefficient (ADC) and intravoxel incoherent motion parameters exhibited any significant correlation with standardized uptake values (SUV) in patients with nasopharyngeal carcinoma (NPC). A total of 35 patients with NPC underwent whole body PET­computed tomography (CT) and head and neck MR imaging (MRI) scans using the PET/CT­MRI system. Image quality, lesion conspicuity and the diagnostic confidence of PET/CT, T1 weighted (T1w) PET/MR and T2w PET/MR imaging were assessed. The true diffusion coefficient (D), the pseudo­diffusion coefficient or diffusion within the microcirculation (D*), and the perfusion fraction or the contribution of water moving in the capillaries (f), and ADC, were calculated. The correlation between the ADC, D*, D and f values and the SUV were analyzed using Pearson's correlation analysis. Similar image quality was obtained using PET/CT, T1w PET/MR and T2w PET/MR imaging. However, the T1w PET/MR and T2w PET/MR imaging were more effective than PET/CT in analyzing the lesion conspicuity of the primary tumors and lymph nodes. In addition, T2w PET/MR imaging was more efficient than T1w PET/MR imaging in analyzing primary tumors and lymph nodes. Pearson's correlation analysis showed no significant correlation between the SUV and ADC, and D*, D and f values in NPC. The present results suggested that the application of PET/MR is feasible and could serve as a reliable alternative to PET/CT, while SUV and ADC, D*, D and f values were identified as independent biomarkers in NPC.