Effects of Short Term Metformin Treatment on Brown Adipose Tissue Activity and Plasma Irisin Levels in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial.

Polycystic ovary syndrome (PCOS) is a chronic dysfunction associated with obesity and metabolic disorders that can be ameliorated by treatment with metformin. Brown adipose tissue (BAT) has been recently identified in adult humans, and irisin is a myokine that induces BAT formation. The aim of this randomized controlled trial was to evaluate whether a short term treatment with metformin alters BAT activity and plasma irisin levels in women with PCOS. The participants were randomly assigned to receive metformin (1500 mg/day, n=21) or placebo (n=24) during 60 days. BAT activity was assessed by 18F-FDG positron emission tomography-computed tomography (PET-CT) and plasma irisin levels were measured by enzyme immunoassay. The groups were similar in age, body measures, metabolic profile and PCOS phenotypes. BAT activity did not change significantly in the women treated with metformin (median Δ SUVmax=-0.06 g/ml, interquartile interval -2.81 to 0.24 g/ml, p=0.484, Wilcoxon's test) or placebo (median Δ SUVmax=0.98 g/ml, interquartile interval -2.94 to 4.60 g/ml, p=0.386). In addition, plasma irisin levels remained unchanged in the groups treated with metformin (median Δ=-98 ng/ml, interquartile interval -366 to 60 ng/ml, p=0.310) and placebo (median Δ=28 ng/ml, interquartile interval -1260 to 215 ng/ml, p=0.650). These results suggest that in PCOS women BAT activity and plasma irisin levels may not change after a brief treatment with metformin.

18F-FDG PET/CT as a prognostic factor in penile cancer.

PURPOSE: Penile cancer (PC) is a rare neoplasm with an aggressive behavior and variable prognosis. Lymph node (LN) involvement and pathological features of the primary lesion have been proven to be the most important survival factors. Positron emission tomography/computed tomography with fluorodeoxyglucose labelled with fluorine-18 (18F-FDG PET/CT) provides information on tumor staging and works as a prognostic factor, with promising results in other carcinomas. The aim of the present study is to evaluate PET/CT as a prognostic factor in PC. METHODS: Fifty-five patients (mean age 56.6 y) diagnosed with penile squamous cell carcinoma were prospectively evaluated from 2012 to 2014. All subjects underwent 18F-FDG PET/CT before treatment and were regularly followed after surgery. RESULTS: Out of the 53 patients selected, 17 (32.1%) had localized disease (cT1-2) and 24 (45.3%) had palpable nodes (cN+). Partial penile amputation was performed in 38 patients (71.7%) and inguinal lymphadenectomy (LND) in 30 (56.6%). From the LND group, 16 (53.3%) presented with positive neoplastic cells (pN+). Patients with more aggressive disease had a significantly (p = 0.019) higher 18F-FDG tumor uptake (pSUVmax), while inguinal LN uptake (nSUVmax) was able to recognize metastatic LN (p = 0.039). Some pathological prognostic features, when presented, have shown significant changes in pSUVmax values. Receiver operating characteristic (ROC) curves were performed and specific cutoff values of pSUVmax were evaluated to determine sensitivity and specificity. Regarding regional LNs, PET/CT presented a 76.2% accuracy in cN+ patients. After a 39-month follow up, pSUVmax of 16.6 (p = 0.0001) and nSUVmax of 6.5 (p = 0.019) were established as the ideal values to predict cancer-specific survival. The multivariate analysis confirmed nSUVmax as a predictor for LN metastasis (p = 0.043) and pSUVmax as a mean to estimate survival rate (p = 0.05). CONCLUSION: This study showed promising results on the use of 18F-FDG PET/CT as a prognostic tool for PC, using specific cutoff values of pSUVmax and nSUVmax.

Malignant phenotype and two SDHD mutations in a family with paraganglioma syndrome type 1.

BACKGROUND: Paraganglioma syndrome type 1 (PGL1) is a rare autosomal dominant syndrome associated with multiple, overwhelmingly benign, pheochromocytomas and paragangliomas, attributed to SDHD gene mutations. OBJECTIVE: Clinically and molecularly characterize a family with uncommon malignant phenotype of paragangliomas attributed to two seemingly pathogenic SDHD germline mutations. MATERIALS & METHODS: The proband presented with large bilateral carotid body tumours and family history of cervical masses in his five siblings. All family members underwent clinical examination, imaging studies (18F-FDG PET/CT) and genotyping of relevant genes. The proband was diagnosed with locally advanced paraganglioma; his hypertensive, otherwise asymptomatic father, had locally advanced pheochromocytoma and his three siblings showed multiple head and neck masses, confirmed to be paragangliomas with local metastasis. All affected patients carried two germline mutations in the SDHD gene; a previously reported nonsense mutation in exon 1 (p.Trp5X) and a novel missense mutation in exon 2 (p.Pro53Leu), highly deleterious by in silico analysis. Allelic loss at the SDHD locus was not shown for any of the analysed tumours. CONCLUSIONS: This is a rare case of malignant PGL1 with seemingly double pathogenic mutations in the SDHD gene, highlighting the possibility that the presence of both mutations is associated with the more aggressive phenotype.

Phase 2 trial of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced cervical cancer.

BACKGROUND: Cisplatin-based chemoradiation (CRT) is the standard treatment for patients with locally advanced cervical cancer. Epidermal growth factor receptor (EGFR) is frequently overexpressed in cervical cancer, and EGFR inhibition itself has antitumor effects and potentiates CRT. Results of a previous phase 1 trial of the EGFR inhibitor erlotinib combined with cisplatin-based CRT (E + CRT) recommended a phase 2 erlotinib dose of 150 mg/day. METHODS: Eligibility criteria included International Federation of Gynecology and Obstetrics stage IIB to IIIB epidermoid cervical cancer, no prior therapy, and an Eastern Cooperative Oncology Group performance status of 0 to 2. Patients received erlotinib at a dose of 150 mg/day 1 week before and in combination with cisplatin (40 mg/m(2) administered weekly for 5 cycles) and radiotherapy (4500 centigrays in 25 fractions), followed by brachytherapy (4 fractions at a dose of 600 centigrays weekly). RESULTS: A total of 36 patients completed treatment with E + CRT. The median duration of therapy was 77 days and the median follow-up period was 59.3 months. The therapy was well tolerated overall, and 34 patients (94.4%) achieved a complete response. The 2-year and 3-year cumulative overall and progression-free survival rates were 91.7% and 80.6% and 80% and 73.8%, respectively. CONCLUSIONS: Treatment with E + CRT appears to be safe and exerts significant activity against locally advanced cervical cancer. To the best of the authors' knowledge, this is the first study to date to demonstrate that a target agent has promising activity against locally advanced cervical cancer.

(11)C-Choline PET/CT in patients with hormone-resistant prostate cancer showing biochemical relapse after radical prostatectomy.

PURPOSE: To determine the diagnostic efficacy of (11)C-choline PET/CT in patients with prostate cancer (PC) after radical prostatectomy who presented with increasing PSA levels during follow-up in spite of being on hormone treatment (HT), and therefore showing HT resistance. METHODS: We evaluated a large series of 157 consecutive PC patients previously treated by radical prostatectomy who presented with biochemical recurrence with increasing PSA levels in spite of ongoing HT (HT-resistant patients). At the time of (11)C-choline PET/CT, the mean value of trigger PSA level was 8.3 (range 0.2 - 60.6 ng/mL), the mean PSA doubling time (PSAdt) was 5.3 (range 0.4 - 35 months), and the mean PSA velocity (PSAvel) was 22.1 ng/mL/year (range 0.12 - 82 ng/mL/year). (11)C-Choline PET/CT was performed following a standard procedure at our centre to investigate increasing PSA levels, either as the first imaging procedure or in patients with negative conventional imaging. At the time of (11)C-choline PET/CT all patients were receiving HT (61 were receiving monotherapy and 96 multidrug therapy). PET-positive findings were validated by: (a) transrectal US-guided biopsy in patients with recurrence in the prostatic bed, (b) surgical pelvic lymphadenectomy, (c) other imaging modalities, including repeated (11)C-choline PET/CT, performed during a minimum follow-up of 12-months. RESULTS: (11)C-Choline PET/CT showed positive findings in 104 of the 157 patients (66 %). (11)C-choline PET/CT detected: a single lesion in 40 patients (7 in the prostate bed, 10 in lymph nodes, 22 in bone, 1 at another site); two lesions in 18 patients (7 in lymph nodes, 7 in bone, 4 in both lymph nodes and bone); three or four lesions in 7 patients (4 in lymph nodes, 2 in bone, 1 at another site); and more than four lesions in the remaining 39 patients (2 in the prostate bed, 12 in lymph nodes, 12 in bone, 11 in both lymph nodes and bone, 2 at other sites). In (11)C-choline PET-negative patients, the mean values of trigger PSA, PSAdt and PSAvel were 3.8 ng/mL (range 0.2-11.9 ng/mL) 7.0 months (range 1.21 - 35 months) and 5.8 ng/mL/year (range 0.12 - 30.1) respectively, while in (11)C-Choline-PET-positive patients they were 10.5 ng/mL (range 0.2 - 60.6), 4.4 months (range 0.4 - 19.7) and 15.9 ng/mL/year (range 0.5 - 82.0) respectively. The differences between PET-negative and PET-positive patients were statistically significant for all these parameters: trigger PSA, p < 0.01; PSAdt, p < 0.01; PSAvel, p = 0.03. CONCLUSION: In our patient population, (11)C-choline PET/CT was able to detect relapsed disease in a large proportion of HT-resistant PC patients during HT. These data, obtained in a large series, suggest that HT withdrawal before performing a (11)C-choline PET/CT scan may not be necessary for the detection of recurrent disease if PSA levels are increasing and PSA kinetics are rapid.

Prostate cancer tissue classification by multiphoton imaging, automated image analysis and machine learning.

Prostate carcinoma, a slow-growing and often indolent tumour, is the second most commonly diagnosed cancer among men worldwide. The prognosis is mainly based on the Gleason system through prostate biopsy analysis. However, new treatment and monitoring strategies depend on a more precise diagnosis. Here, we present results by multiphoton imaging for prostate tumour samples from 120 patients that allow to obtain quantitative parameters leading to specific tumour aggressiveness signatures. An automated image analysis was developed to recognise and quantify stromal fibre and neoplastic cell regions in each image. The set of metrics was able to distinguish between non-neoplastic tissue and carcinoma areas by linear discriminant analysis and random forest with accuracy of 89% ± 3%, but between Gleason groups of only 46% ± 6%. The reactive stroma analysis improved the accuracy to 65% ± 5%, clearly demonstrating that stromal parameters should be considered as additional criteria for a more accurate diagnosis.

KETO[18F]FDG -VAP-P1: In vivo studies of a potential PET radiotracer for diagnosis of inflammation.

The biodistribution of radiotracer peptide KETO[18F]FDG-VAP-P1 was evaluated by ex vivo radiation count in organs and in vivo PET imaging of healthy mice. The peptide was quickly eliminated by the kidneys. The local inflammation caused by a sterile polyurethane sponge was evaluated by PET images. In addition, dosimetry estimates of KETO[18F]FDG-VAP-P1 tracer are determined for mice using Monte Carlo simulations. Thus, the results of this study indicate that KETO[18F]FDG-VAP-P1 is a potential radiotracer for inflammation imaging.

PET/CT and inflammatory mediators in systemic sclerosis-associated interstitial lung disease.

OBJECTIVE: To investigate the correlation of HRCT findings with pulmonary metabolic activity in the corresponding regions using 18F-FDG PET/CT and inflammatory markers in patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD). METHODS: This was a cross-sectional study involving 23 adult patients with SSc-associated ILD without other connective tissue diseases. The study also involved 18F-FDG PET/CT, HRCT, determination of serum chemokine levels, clinical data, and pulmonary function testing. RESULTS: In this cohort of patients with long-term disease (disease duration, 11.8 ± 8.7 years), a nonspecific interstitial pneumonia pattern was found in 19 (82.6%). Honeycombing areas had higher median standardized uptake values (1.95; p = 0.85). Serum levels of soluble tumor necrosis factor receptor 1, soluble tumor necrosis factor receptor 2, C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine ligand 10 were higher in SSc patients than in controls. Serum levels of CCL2-a marker of fibroblast activity-were correlated with pure ground-glass opacity (GGO) areas on HRCT scans (p = 0.007). 18F-FDG PET/CT showed significant metabolic activity for all HRCT patterns. The correlation between serum CCL2 levels and GGO on HRCT scans suggests a central role of fibroblasts in these areas, adding new information towards the understanding of the mechanisms surrounding cellular and molecular elements and their expression on HRCT scans in patients with SSc-associated ILD. CONCLUSIONS: 18F-FDG PET/CT appears to be unable to differentiate the intensity of metabolic activity across HRCT patterns in chronic SSc patients. The association between CCL2 and GGO might be related to fibroblast activity in these areas; however, upregulated CCL2 expression in the lung tissue of SSc patients should be investigated in order to gain a better understanding of this association.

FDG PET/CT patterns of treatment failure of malignant pleural mesothelioma: relationship to histologic type, treatment algorithm, and survival.

PURPOSE: This study investigated the diagnostic performance and prognostic value of fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in suspected malignant pleural mesothelioma (MPM) recurrence, in the context of patterns and intensity of FDG uptake, histologic type, and treatment algorithm. METHODS: Fifty patients with MPM underwent FDG PET/CT for restaging 11 ± 6 months after therapy. Tumor relapse was confirmed by histopathology, and by clinical evolution and subsequent imaging. Progression-free survival was defined as the time between treatment and the earliest clinical evidence of recurrence. Survival after FDG PET/CT was defined as the time between the scan and death or last follow-up. Overall survival was defined as the time between initial treatment and death or last follow-up date. RESULTS: Treatment failure was confirmed in 42 patients (30 epithelial and 12 non-epithelial MPM). Sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for FDG PET/CT were 97.6, 75, 94, 86, and 95.3%, respectively. FDG PET/CT evidence of single site of recurrence was observed in the ipsilateral hemithorax in 18 patients (44%), contralaterally in 2 (5%), and in the abdomen in 1 patient (2%). Bilateral thoracic relapse was detected in three patients (7%). Simultaneous recurrence in the ipsilateral hemithorax and abdomen was observed in ten (24%) patients and in seven (17%) in all three cavities. Unsuspected distant metastases were detected in 11 patients (26%). Four patterns of uptake were observed in recurrent disease: focal, linear, mixed (focal/linear), and encasing, with a significant difference between the intensity of uptake in malignant lesions compared to benign post-therapeutic changes. Lesion uptake was lower in patients previously treated with more aggressive therapy and higher in intrathoracic lesions of patients with distant metastases. FDG PET/CT helped in the selection of 12 patients (29%) who benefited from additional previously unplanned treatment at the time of failure. Multivariate analysis showed that histologic type remained the only independent predictor of progression-free survival. Survival after relapse was independently predicted by the pattern of FDG uptake and PET nodal status, and overall survival by the maximum standard uptake value. CONCLUSION: FDG PET/CT is an accurate modality to diagnose and to estimate the extent of locoregional and distant MPM recurrence, and it carries independent prognostic value. Once the disease recurs, survival outcomes seem to be independent of histologic type and highly dependent on the intensity of lesion uptake and on the pattern of metabolically active disease in FDG PET/CT. Our observations should be considered limited to patients treated surgically with or without perioperative therapies and should not be extrapolated to those unresectable cases treated with chemotherapy alone.

Motion artifacts occurring at the lung/diaphragm interface using 4D CT attenuation correction of 4D PET scans.

For PET/CT, fast CT acquisition time can lead to errors in attenuation correction, particularly at the lung/diaphragm interface. Gated 4D PET can reduce motion artifacts, though residual artifacts may persist depending on the CT dataset used for attenuation correction. We performed phantom studies to evaluate 4D PET images of targets near a density interface using three different methods for attenuation correction: a single 3D CT (3D CTAC), an averaged 4D CT (CINE CTAC), and a fully phase matched 4D CT (4D CTAC). A phantom was designed with two density regions corresponding to diaphragm and lung. An 8 mL sphere phantom loaded with 18F-FDG was used to represent a lung tumor and background FDG included at an 8:1 ratio. Motion patterns of sin(x) and sin4(x) were used for dynamic studies. Image data was acquired using a GE Discovery DVCT-PET/CT scanner. Attenuation correction methods were compared based on normalized recovery coefficient (NRC), as well as a novel quantity "fixed activity volume" (FAV) introduced in our report. Image metrics were compared to those determined from a 3D PET scan with no motion present (3D STATIC). Values of FAV and NRC showed significant variation over the motion cycle when corrected by 3D CTAC images. 4D CTAC- and CINE CTAC-corrected PET images reduced these motion artifacts. The amount of artifact reduction is greater when the target is surrounded by lower density material and when motion was based on sin4(x). 4D CTAC reduced artifacts more than CINE CTAC for most scenarios. For a target surrounded by water equivalent material, there was no advantage to 4D CTAC over CINE CTAC when using the sin(x) motion pattern. Attenuation correction using both 4D CTAC or CINE CTAC can reduce motion artifacts in regions that include a tissue interface such as the lung/diaphragm border. 4D CTAC is more effective than CINE CTAC at reducing artifacts in some, but not all, scenarios.

Long-term metabolic evolution of brain metastases with suspected radiation necrosis following stereotactic radiosurgery: longitudinal assessment by F-DOPA PET.

BACKGROUND: The evolution of radiation necrosis (RN) varies depending on the combination of radionecrotic tissue and active tumor cells. In this study, we characterized the long-term metabolic evolution of RN by sequential PET/CT imaging with 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (F-DOPA) in patients with brain metastases following stereotactic radiosurgery (SRS). METHODS: Thirty consecutive patients with 34 suspected radionecrotic brain metastases following SRS repeated F-DOPA PET/CT every 6 months or yearly in addition to standard MRI monitoring. Diagnoses of local progression (LP) or RN were confirmed histologically or by clinical follow-up. Semi-quantitative parameters of F-DOPA uptake were extracted at different time points, and their diagnostic performances were compared with those of corresponding contrast-enhanced MRI. RESULTS: Ninety-nine F-DOPA PET scans were acquired over a median period of 18 (range: 12-66) months. Median follow-up from the baseline F-DOPA PET/CT was 48 (range 21-95) months. Overall, 24 (70.6%) and 10 (29.4%) lesions were classified as RN and LP, respectively. LP occurred after a median of 18 (range: 12-30) months from baseline PET. F-DOPA tumor-to-brain ratio (TBR) and relative standardized uptake value (rSUV) increased significantly over time in LP lesions, while remaining stable in RN lesions. The parameter showing the best diagnostic performance was rSUV (accuracy = 94.1% for the optimal threshold of 1.92). In contrast, variations of the longest tumor dimension measured on contrast-enhancing MRI did not distinguish between RN and LP. CONCLUSION: F-DOPA PET has a high diagnostic accuracy for assessing the long-term evolution of brain metastases following SRS.

Abdominal masses sampled at PET/CT-guided percutaneous biopsy: initial experience with registration of prior PET/CT images.

PURPOSE: To establish the feasibility of performing combined positron emission tomography (PET)/computed tomography (CT)-guided biopsy of abdominal masses by using previously acquired PET/CT images registered with intraprocedural CT images. MATERIALS AND METHODS: In this HIPAA-compliant institutional review board-approved study, 14 patients underwent clinically indicated percutaneous biopsy of abdominal masses (mean size, 3.3 cm; range, 1.2-5.0 cm) in the liver (n = 6), presacral soft tissue (n = 3), retroperitoneal lymph nodes (n = 2), spleen (n = 2), and pancreas (n = 1). PET/CT images obtained no more than 62 days (mean, 18.3 days) before the biopsy procedure were registered with intraprocedural CT images by using image registration software. The registered images were used to plan the procedure and help target the masses. RESULTS: The image registrations were technically successful in all but one patient, who had severe scoliosis. The remaining 13 biopsy procedures yielded diagnostic results, which were positive for malignancy in 10 cases and negative in three cases. CONCLUSION: PET/CT-guided abdominal biopsy with use of prior PET/CT images registered with intraprocedural CT scans is feasible and may be helpful when fluorine 18 fluorodeoxyglucose-avid masses that are not seen sufficiently with nonenhanced CT are sampled at biopsy.

Brown adipose tissue activity is reduced in women with polycystic ovary syndrome.

Objective: To evaluate whether brown adipose tissue (BAT) activity is altered in women with polycystic ovary syndrome (PCOS), and whether BAT activity correlates with plasma levels of irisin, a myokine that can induce BAT formation. Design: We performed a cross-sectional study including women with PCOS (n = 45) and a healthy control group (n = 25) matched by age and body mass index (BMI). Methods: BAT activity was measured using 18F-FDG positron emission tomography-computed tomography (PET-CT) and plasma irisin levels were measured by a validated enzyme immunoassay. Results: Total BAT activity was significantly reduced in women with PCOS (maximal standardized uptake value (SUVmax): median 7.4 g/mL, interquartile range 0.9-15.4) compared to controls (median 13.0 g/mL, interquartile range 4.7-18.4, P = 0.047). However, this difference was no longer significant after adjustment for waist circumference, a surrogate marker of central adiposity. In the PCOS group, BAT activity correlated negatively with BMI (Spearman's r = -0.630, P = 0.000) and waist circumference (r = -0.592, P = 0.000) but not with plasma irisin levels. Conclusions: BAT activity was reduced in women with PCOS possibly due to increased central adiposity. In PCOS women, BAT activity did not correlate with plasma irisin levels.

Evaluation of the combined effects of target size, respiratory motion and background activity on 3D and 4D PET/CT images.

Gated (4D) PET/CT has the potential to greatly improve the accuracy of radiotherapy at treatment sites where internal organ motion is significant. However, the best methodology for applying 4D-PET/CT to target definition is not currently well established. With the goal of better understanding how to best apply 4D information to radiotherapy, initial studies were performed to investigate the effect of target size, respiratory motion and target-to-background activity concentration ratio (TBR) on 3D (ungated) and 4D PET images. Using a PET/CT scanner with 4D or gating capability, a full 3D-PET scan corrected with a 3D attenuation map from 3D-CT scan and a respiratory gated (4D) PET scan corrected with corresponding attenuation maps from 4D-CT were performed by imaging spherical targets (0.5-26.5 mL) filled with (18)F-FDG in a dynamic thorax phantom and NEMA IEC body phantom at different TBRs (infinite, 8 and 4). To simulate respiratory motion, the phantoms were driven sinusoidally in the superior-inferior direction with amplitudes of 0, 1 and 2 cm and a period of 4.5 s. Recovery coefficients were determined on PET images. In addition, gating methods using different numbers of gating bins (1-20 bins) were evaluated with image noise and temporal resolution. For evaluation, volume recovery coefficient, signal-to-noise ratio and contrast-to-noise ratio were calculated as a function of the number of gating bins. Moreover, the optimum thresholds which give accurate moving target volumes were obtained for 3D and 4D images. The partial volume effect and signal loss in the 3D-PET images due to the limited PET resolution and the respiratory motion, respectively were measured. The results show that signal loss depends on both the amplitude and pattern of respiratory motion. However, the 4D-PET successfully recovers most of the loss induced by the respiratory motion. The 5-bin gating method gives the best temporal resolution with acceptable image noise. The results based on the 4D scan protocols can be used to improve the accuracy of determining the gross tumor volume for tumors in the lung and abdomen.

18F-DOPA uptake parameters in glioma: effects of patients' characteristics and prior treatment history.

OBJECTIVE: In amino acid positron emission tomography brain tumour imaging, tumour-to-background uptake parameters are often used for treatment monitoring. We studied the effects of patients' characteristics and anticancer treatments on 18F-fluoro-l-phenylalanine uptake of normal brain and tumour lesions, with particular emphasis on temozolomide (TMZ) chemotherapy. METHODS: 155 studies from 120 patients with glioma were analysed. Average uptake of normal background (standardized uptake value, SUVbckgr) and basal ganglia (SUVbg), as well as tumour-to-brain ratios (TBR) were compared between positron emission tomography/CT studies acquired before (Group A, n = 48), after (Group B, n = 50) or during (Group C, n = 57) TMZ treatment, using analysis of variance. RESULTS: Overall, mean SUVbckgr and mean SUVbg were 1.06 ± 0.26 and 2.12 ± 0.47, respectively. Female had significantly higher SUVbckgr (p = 0.002) and SUVbg (p = 0.012) than male patients. Age showed a positive correlation with SUVbg (p = 0.001). In the overall cohort, there were significant effects of TMZ on SUVbckgr (p = 0.0237) and TBR (p = 0.0138). In particular, SUVbckgr was lower in Group C than in Group B (1.00 ± 0.25 vs 1.14 ± 0.31, p = 0.0173). Significant variations of SUVbckr could be observed in female only. TBR was significantly higher in Group C than in Group B (2.37 ± 0.54 vs 2.06 ± 0.38, p = 0.010). Variations of SUVbg between groups slightly missed significance (p = 0.0504). CONCLUSION: Temozolomide chemotherapy and patients' characteristics, including gender and age, affect physiological [18F]-fluoro-l-phenylalanine uptake and, consequently, the calculation of TBRs. Advances in knowledge: For the first time, the effects of past or concurrent temozolomide chemotherapy on brain physiological amino acid uptake have been investigated. Such effects are relevant and should be taken into account when evaluating tumour-to-background ratios.

Use of machine learning to predict cognitive performance based on brain metabolism in Neurofibromatosis type 1.

Neurofibromatosis Type 1 (NF1) can cause a wide range of cognitive deficits, but its underlying nature is still unknown. We investigated the correlation between cognitive performance and specific patterns of resting-state brain metabolism in a NF1 sample. Sixteen individuals diagnosed with NF1 underwent 18F-FDG PET/CT brain imaging followed by a neuropsychological assessment. Principal component analysis was performed on 17 measures of cognitive function and a machine learning approach based on Gaussian Process Regression was used to individually predict the components that represented most of the variance in the neuropsychological data. The accuracy of the method was estimated using leave-one-out cross-validation and its significance through permutation testing. We found that only the first component could be accurately predicted from resting state metabolism (r = 0.926, p<0.001). Multiple and heterogeneous measures contribute to the first component, mainly WISC/WAIS Procedure and Verbal IQ, verbal memory and fluency. Considering the accurate prediction of measures of neuropsychological performance based on brain metabolism in NF1 patients, this suggests an underlying metabolic pattern that relates to cognitive performance in this group.

Raman spectroscopy with a 1064-nm wavelength laser as a potential molecular tool for prostate cancer diagnosis: a pilot study.

Raman spectroscopy is widely used to investigate the structure and property of the molecules from their vibrational transitions and may allow for the diagnosis of cancer in a fast, objective, and nondestructive manner. This experimental study aims to propose the use of the 1064-nm wavelength laser in a Raman spectroscopy and to evaluate its discrimination capability in prostate cancer diagnosis. Seventy-four spectra from patients who underwent radical prostatectomy were evaluated. The acquired signals were filtered, normalized, and corrected for possible oscillations in the laser intensity and fluorescence effects. Wilcoxon tests revealed significant differences between the benign and malign samples associated with the deformation vibration characteristic of nucleic acids, proteins, and lipids. A classifier based on support vector machines was able to predict the Gleason scores of the samples with 95% of accuracy, opening a perspective for the use of the 1064-nm excitatory wavelength in prostatic cancer diagnosis.

Individualized threshold for tumor segmentation in 18F-FDG PET/CT imaging: The key for response evaluation of neoadjuvant chemoradiation therapy in patients with rectal cancer?

INTRODUCTION: The standard treatment for locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiation followed by radical surgery. Regardless the extensive use of SUVmax in 18F-FDG PET tumor uptake as representation of tumor glycolytic consumption, there is a trend to apply metabolic volume instead. Thus, the aim of the present study was to evaluate a noninvasive method for tumor segmentation using the 18F-FDG PET imaging in order to predict response to neoadjuvant chemoradiation therapy in patients with rectal cancer. METHOD: The sample consisted of stage II and III rectal cancer patients undergoing 18F-FDG PET/CT examination before and eight weeks after neoadjuvant therapy. An individualized tumor segmentation methodology was applied to generate tumor volumes (SUV2SD) and compare with standard SUVmax and fixed threshold (SUV40%, SUV50% and SUV60%) pre- and post-therapy. Therapeutic response was assessed in the resected specimens using Dworak's protocol recommendations. Several variables were generated and compared with the histopathological results. RESULTS: Seventeen (17) patients were included and analyzed. Significant differences were observed between responders (Dworak 3 and 4) and non-responders for SUVmax-2 (p<0.01), SUV2SD-2 (p<0.05), SUV40%-2 (p<0.05), SUV50%-2 (p<0.05) and SUV60%-2 (p<0.05). ROC analyses showed significant areas under the curve (p<0.01) for the proposed methodology with sensitivity and specificity varying from 60% to 83% and 73% to 82%, respectively. CONCLUSION: The present study confirmed the predictive power of the variables using a noninvasive individualized methodology for tumor segmentation based on 18F-FDG PET/CT imaging for response evaluation in patients with rectal cancer after neoadjuvant chemoradiation therapy.

Spinal cord hypometabolism associated with infection by human T-cell lymphotropic virus type 1(HTLV-1).

BACKGROUND: HTLV-1 infection is endemic in Brazil. About 1 to 2% of the Brazilian population is estimated to be infected, but most infected HTLV-1 individuals do not know about their own infection, which favors the continuity of sexual and vertical virus transmission. In addition, HTLV-1 associated central nervous system diseases and their pathophysiologic mechanisms are not fully understood. This study aimed to evaluate the correlation of spinal cord metabolism, viral and inflammatory profiles with features of neurological presentation in HTLV-1 infected individuals. METHODOLOGY: This is a cross-sectional study of a cohort including 48 HTLV-1 infected individuals clinically classified as asymptomatic-AG (N = 21), symptomatic-SG (N = 11) and HAM/TSP-HG (N = 16) and a nested case-control study with HTLV-1 infected individuals-HIG (N = 48) and HTLV-1 non infected controls-CG (N = 30) that had their spinal cord analysed by Positron Emission Tomography with 18F-Fluordeoxyglucose (18F-FDG PET/CT). HTLV-1 infected individuals had 18F-FDG PET/CT results analyzed with clinical and demographic data, proviral load, cytokines and chemokines in the blood and cerebrospinal fluid (CSF). PRINCIPAL FINDINGS: 18F-FDG PET/CT showed hypometabolism in the thoracic spinal cord in HTLV-1 infected individuals. The method had an accuracy of 94.4% to identify HAM/TSP. A greater involvement of the thoracic spinal cord was observed, although hypometabolism was also observed in the cervical spinal cord segment in HTLV-1 infected individuals. Individuals with HAM/TSP showed a pro-inflammatory profile in comparison to asymptomatic and symptomatic groups, with a higher level of Interferon-inducible T-cell alpha chemoattractant (ITAC/CXCL11), IL-6, IL-12p70 in the plasma; and ITAC, IL-4, IL-5, IL-8 (CXCL8) and TNF-alpha in the CSF. Using regression, thoracic spinal cord SUV (standardized uptake value) and CSF ITAC level were identified as the HAM/TSP predictors in the multivariate model. CONCLUSIONS: 18F-FDG PET/CT imaging showed spinal cord hypometabolism in most HTLV-1 infected individuals, even in the asymptomatic HTLV-1 group. Thoracic spinal cord hypometabolism and CSF-ITAC levels were identified predictors of HAM/TSP. SIGNIFICANCE: Our findings suggested that in most HTLV-1 infected individuals there was compromise of central nervous system (CNS) structures despite of the lack of clinical symptoms. To explain the found hypometabolism, the role of microcirculatory and metabolic factors in the pathogenesis of neurological diseases associated with HTLV-1 infection must be further investigated. It is paramount to evaluate the central nervous function and to compare the performance among HTLV-1 infected individuals considered asymptomatic to the uninfected controls.

Temporal change in human nicotinic acetylcholine receptor after smoking cessation: 5IA SPECT study.

UNLABELLED: Nicotinic acetylcholine receptors (nAChRs) are of great interest because they are implicated in various brain functions. They also are thought to play an important role in nicotine addiction of smokers. Chronic (-)-nicotine, a nAChR agonist, treatment in mice and rats elicits a dose-dependent increase in nAChRs in the brain. Upregulation of nAChRs in postmortem human brains of smokers has also been reported. However, changes in nAChRs after cigarette smoking cessation in humans are poorly understood. The aim of this study was to detect the dynamic changes of nAChRs after smoking and smoking cessation in the brains of living subjects. METHODS: We performed 5-(123)I-iodo-A-85380 ((123)I-5IA) SPECT on nonsmokers and smokers (n = 16) who had quit smoking for 4 h, 10 d, and 21 d and calculated and compared distribution volumes (Vt) of (123)I-5IA. RESULTS: The binding potential of nAChRs (Vt of (123)I-5IA) in the brains of smokers decreased by 33.5% +/- 10.5% after 4 h of smoking cessation, increased by 25.7% +/- 9.2% after 10 d of smoking cessation, and decreased to the level of nonsmokers after 21 d of smoking cessation. CONCLUSION: Because the upregulation of the nAChRs of the smokers after chronic exposure of the nicotine was downregulated to the nonsmokers' level by around 21 d after smoking cessation, the upregulation is a temporary effect. The decrease in nicotinic receptors to nonsmoker levels may be the breaking point during the nicotine withdrawal period.