The brain cognitive reserve hypothesis: A review with emphasis on the contribution of nuclear medicine neuroimaging techniques.

Neuropathological and clinical evidence indicates that the clinical expression of Alzheimer's disease (AD) occurs as neuropathology exceeds the brain reserve capacity. The brain or cognitive reserve (BCR) hypothesis states that high premorbid intelligence, education, and an active and stimulating lifestyle provide reserve capacity, which acts as a buffer against the cognitive deficits due to accumulating neuropathology. Neuroimaging studies that assessed the BCR hypothesis are critically reviewed with emphasis on study design and statistical analysis. Many studies were performed in the last two decades owing to the increasing availability of positron emission tomography (PET) and PET/computed tomography scanners and to the synthesis of new radiopharmaceuticals, including tracers for amyloid and tau proteins. Studies with different tracers provided complementary consistent results supporting the BCR hypothesis. Many studies were appropriately designed with a measure of reserve, a measure of brain anatomy/function/neuropathology, and a measure of cognitive functions that are necessary. Most of the early studies were performed with PET and [ 18 F]fluorodeoxyglucose, and occasionally with [ 15 O]water, reporting a significant association between higher occupation/education and lower glucose metabolism (blood flow) in associative temporo-parietal cortex in patients with AD and also in patients with MCI, after correcting for the degree in the cognitive impairment. On the contrary, performances on several neuropsychological tests increased with increasing education for participants with elevated [ 11 C]PiB uptake. Studies with the tracers specific for tau protein showed that patients with AD with elevated tau deposits had higher cognitive performances compared with patients with similar levels of tau deposits. BCR in AD is also associated with a preserved cholinergic function. The BCR hypothesis has been validated with methodologically sound study designs and sophisticated neuroimaging techniques using different radiotracers and providing an explanation for neuropathological and clinical observations on patients with AD.

Amyloid burden identifies neuropsychological phenotypes at increased risk of progression to Alzheimer's disease in mild cognitive impairment patients.

PURPOSE: The extent of amyloid burden associated with cognitive impairment in amnestic mild cognitive impairment is unknown. The primary aim of the study was to determine the extent to which amyloid burden is associated to the cognitive impairment. The secondary objective was to test the relationship between amyloid accumulation and memory or cognitive impairment. MATERIALS AND METHODS: In this prospective study 66 participants with amnestic mild cognitive impairment underwent clinical, neuropsychological and PET amyloid imaging tests. Composite scores assessing memory and non-memory domains were used to identify two clinical classes of neuropsychological phenotypes expressing different degree of cognitive impairment. Detection of amyloid status and definition of optimal amyloid ± cutoff for discrimination relied on unsupervised k-means clustering method. RESULTS: Threshold for identifying low and high amyloid retention groups was of SUVr = 1.3. Aß + participants showed poorer global cognitive and episodic memory performance than subjects with low amyloid deposition. Aß positivity significantly identified individuals with episodic memory impairment with a sensitivity and specificity of 80 and 79%, (χ2 = 21.48; P < 0.00001). Positive and negative predictive values were 82 and 76%, respectively. Amyloid deposition increased linearly as function of memory impairment with a rate of 0.13/ point of composite memory score (R = -44, P = 0.0003). CONCLUSION: The amyloid burden of SUVr = 1.3 allows early identification of subjects with episodic memory impairment which might predict progression from MCI to Alzheimer's disease. TRIAL REGISTRATION: EudraCT 2015-001184-39.

11C-choline PET/CT predicts survival in prostate cancer patients with PSA < 1 NG/ml.

PURPOSE: The main drawback of 11C-choline PET/CT for restaging prostate cancer (PCa) patients with biochemical failure is the relatively low positive detection rate for prostate specific antigen (PSA) < 1 ng/ml. This study assessed whether 11C-choline PET/CT predicts survival in PCa patients with PSA < 1 ng/ml. METHODS: This retrospective study included 210 PCa patients treated with radical prostatectomy who underwent 11C-choline PET/CT from December 1, 2004 to July 31, 2007 due to biochemical failure. PCa-specific survival was estimated using Kaplan-Meier curves. Cox regression analysis was used to evaluate the association between clinicopathologic variables and PCa-specific survival. PCa-specific survival was computed as the interval from radical prostatectomy to PCa-specific death. RESULTS: Median follow-up after radical prostatectomy was 6.9 years (95% confidence interval, CI, 2.0-14.5 years). 11C-choline PET/CT was positive in 20.5% of patients. Median PCa-specific survival was 13.4 years (95% CI, 9.9-16.8 years) in patients with positive 11C-choline PET/CT, and it was not achieved in patients with negative 11C-choline PET/CT (log-rank, chi-square = 15.0, P < 0.001). Ten-year survival probabilities for patients with negative 11C-choline PET/CT and for patients with positive 11C-choline PET/CT were 86.0% (95% CI: 80.7%-91.3%) and 63.6% (95% CI: 54.5-72.7%). At multivariate analysis, only 11C-choline PET/CT significantly predicted PCa-specific survival (hazard ratio = 2.54, 95% CI, 1.05-6.13, P = 0.038). Patients with pathological 11C-choline uptake in the prostatic bed or in pelvic lymph nodes had longer PCa-specific survival in comparison to patients with pathological tracer uptake in the skeleton (log-rank: chi-square = 27.4, P < 0.001). CONCLUSION: Despite the relatively low positive detection rate for PSA < 1 ng/ml, positive 11C-choline PET/CT predicts PCa-specific survival in this low PSA range. As long as more sensitive radiotracers, such as 68Ga-PSMA-11, do not become more widely available, these results might support a broader use of radiolabeled choline in restaging PCa for PSA < 1 ng/ml.

The relationship between local recurrences and distant metastases in prostate cancer: can 11C-choline PET/CT contribute to understand the link?

PURPOSE: Previous studies in prostate cancer (PCa) patients tried to correlate the onset of local recurrence (LR) with the development of distant metastases and formulated, based on theoretical and experimental data, hypotheses linking the two events. We aimed to address this issue with 11C-choline positron emission tomography/computed tomography (PET/CT). METHODS: This retrospective study included 491 PCa patients previously treated with radical prostatectomy who had undergone 11C-choline PET/CT owing to biochemical failure. Further inclusion criteria were availability of clinical and pathological variables for survival analysis. Statistical significance was taken at P < 0.05. RESULTS: Seventy-two patients (14.7%) had evidence of LR at 11C-choline PET/CT. The frequency of LR increased from 13.8% in the interval 0-4 years after prostatectomy, to 23.9% in the 12-16-year interval (P = 0.080). On the contrary, the frequency of lymph node metastases (overall rate in the 0-16 years interval after prostatectomy: 26.3%) and of bone metastases (overall rate: 13.8%) decreased significantly over time. Kaplan-Meier curves showed no significant group difference in the rates of lymph node or bone metastases between patients with LR and patients without LR. LR significantly predicted PCa-specific survival at univariate analysis, but the statistical significance was lost at multivariate analysis. CONCLUSION: We found no differences in the rates of lymph node and bone metastases between patients with and without LR. An inverse time-dependent trend was observed in the frequency of LR on one side and of lymph node and bone metastases on the other side. These findings were discussed in relation to previous theories linking LR to distant metastases and our study design.

Molecular Imaging of Huntington's Disease.

The onset and the clinical progression of Huntington Disease (HD) is influenced by several events prompted by a genetic mutation that affects several organs tissues including different regions of the brain. In the last decades years, Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) helped to deepen the knowledge of neurodegenerative mechanisms that guide to clinical symptoms. Brain imaging with PET represents a tool to investigate the physiopathology occurring in the brain and it has been used to predict the age of onset of the disease and to evaluate the therapeutic efficacy of new drugs. This article reviews the contribution of PET and MRI in the research field on Huntington's disease, focusing in particular on some most relevant achievements that have helped recognize the molecular changes, the clinical symptoms and evolution of the disease. J. Cell. Physiol. 232: 1988-1993, 2017. © 2016 Wiley Periodicals, Inc.

PET and PET/CT with radiolabeled choline in prostate cancer: a critical reappraisal of 20 years of clinical studies.

We here aim to provide a comprehensive and critical review of the literature concerning the clinical applications of positron emission tomography/computed tomography (PET/CT) with radiolabeled choline in patients with prostate cancer (PCa). We will initially briefly summarize the historical context that brought to the synthesis of [11C]choline, which occurred exactly 20 years ago. We have arbitrarily grouped the clinical studies in three different periods, according to the year in which they were published and according to their relation with their applications in urology, radiotherapy and oncology. Studies at initial staging and, more extensively, studies in patients with biochemical failure, as well as factors predicting positive PET/CT will be reviewed. The capability of PET/CT with radiolabeled choline to provide prognostic information on PCa-specific survival will also be examined. The last sections will be devoted to the use of radiolabeled choline for monitoring the response to androgen deprivation therapy, radiotherapy, and chemotherapy. The accuracy and the limits of the technique will be discussed according to the information available from standard validation processes, including biopsy or histology. The clinical impact of the technique will be discussed on the basis of changes induced in the management of patients and in the evaluation of the response to therapy. Current indications to PET/CT, as officially endorsed by guidelines, or as routinely performed in the clinical practice will be illustrated. Emphasis will be made on methodological factors that might have influenced the results of the studies or their interpretation. Finally, we will briefly highlight the potential role of positron emission tomography/magnetic resonance and of new radiotracers for PCa imaging.

[¹¹C]Choline PET/CT predicts survival in hormone-naive prostate cancer patients with biochemical failure after radical prostatectomy.

PURPOSE: Over the last decade, PET/CT with radiolabelled choline has been shown to be useful for restaging patients with prostate cancer (PCa) who develop biochemical failure. The limitations of most clinical studies have been poor validation of [(11)C]choline PET/CT-positive findings and lack of survival analysis. The aim of this study was to assess whether [(11)C]choline PET/CT can predict survival in hormone-naive PCa patients with biochemical failure. METHODS: This retrospective study included 302 hormone-naive PCa patients treated with radical prostatectomy who underwent [(11)C]choline PET/CT from 1 December 2004 to 31 July 2007 because of biochemical failure (prostate-specific antigen, PSA, >0.2 ng/mL). Median PSA was 1.02 ng/mL. PCa-specific survival was estimated using Kaplan-Meier curves. Cox regression analysis was used to evaluate the association between clinicopathological variables and PCa-specific survival. The coefficients of the covariates included in the Cox regression analysis were used to develop a novel nomogram. RESULTS: Median follow-up was 7.2 years (1.4 - 18.9 years). [(11)C]Choline PET/CT was positive in 101 of 302 patients (33%). Median PCa-specific survival after prostatectomy was 14.9 years (95% CI 9.7 - 20.1 years) in patients with positive [(11)C]choline PET/CT. Median survival was not achieved in patients with negative [(11)C]choline PET/CT. The 15-year PCa-specific survival probability was 42.4% (95% CI 31.7 - 53.1%) in patients with positive [(11)C]choline PET/CT and 95.5% (95% CI 93.5 - 97.5 %) in patients with negative [(11)C]choline PET/CT. In multivariate analysis, [(11)C]choline PET/CT (hazard ratio 6.36, 95% CI 2.14 - 18.94, P < 0.001) and Gleason score >7 (hazard ratio 3.11, 95% CI 1.11 - 8.66, P = 0.030) predicted PCa-specific survival. An internally validated nomogram predicted 15-year PCa-specific survival probability with an accuracy of 80%. CONCLUSION: Positive [(11)C]choline PET/CT after biochemical failure predicts PCa-specific survival in hormone-naive PCa patients. Prospective studies are warranted to confirm our results before more extensive use of [(11)C]choline PET/CT for prognostic stratification of PCa patients.

Potentiometric measurement of urinary iodine concentration in patients with thyroid diseases with and without previous exposure to non-radioactive iodine.

BACKGROUND: Extensive application of measurement of urinary iodine concentration (UIC) in several benign and malignant thyroid diseases could profit by the availability of rapid and inexpensive measuring techniques. Aim of this study was to apply a simple and inexpensive commercially available potentiometric method for the quantification of UIC based on iodine-specific ion-selective electrodes (ISE) in patients with thyroid diseases. METHODS: This retrospective study included patients with differentiated thyroid cancer (n=286) and patients with hyperthyroidism of different etiologies (n=203). Within the whole sample (n=489) 20 patients had previously (1 week-6 months) been exposed to iodine overload, either from contrast media (n=8) or amiodarone (n=12). RESULTS: In patients not exposed to iodine, the histogram showed that the distribution of UIC violated normality. The peak of the curve occurred between 5.0 µmol/L and 6.0 µmol/L. Variability was sizeable (percent coefficient of variation, %CV: 66%, 95% confidence interval: 1.48-18.72 µmol/L). The group of exposed patients could be easily distinguished from not exposed patients (median UIC: 47.5 µmol/L vs. 5.42 µmol/L). UIC was significantly correlated to urinary creatinine concentration, but normalization to urinary creatinine increased the inter-subject variability of UIC (%CV=96% vs. 66%). In test-retest studies (n=25) the intra-class correlation coefficient was 0.73 for UIC, 0.82 for creatinine and 0.64 for the UIC: creatinine ratio. CONCLUSIONS: Iodine-specific ISE-based potentiometric methods can be successfully applied as an alternative to existing methods in patients with thyroid diseases. The promising characteristics of the method need to be confirmed in future larger prospective studies.

Relationship between prostate-specific antigen kinetics and detection rate of radiolabelled choline PET/CT in restaging prostate cancer patients: a meta-analysis.

BACKGROUND: The aim of the article was to systematically review published data about the relationship between prostate-specific antigen (PSA) kinetics, including PSA doubling time (PSAdt) and PSA velocity (PSAvel), and detection rate (DR) of positron emission tomography/computed tomography (PET/CT) using radiolabelled choline in restaging prostate cancer (PCa). METHODS: A comprehensive literature search of studies published through July 2013 regarding the relationship between PSA kinetics and DR of radiolabelled choline PET/CT was carried out. Furthermore, a meta-analysis was performed in order to establish the DR of radiolabelled choline PET/CT using different cut-off values of PSAdt (≤ or >6 months) and PSAvel [>1 or ≤1 ng/(mL year) and >2 or ≤2 ng/(mL year)]. Moreover, a pooled analysis to establish whether PSAdt and PSAvel (using the abovementioned cut-off values) may predict positive PET/CT results was carried out. RESULTS: Fourteen articles were selected. The pooled DR of radiolabelled choline PET/CT in restaging PCa was 58% [95% confidence interval (CI) 55-60]. Most articles reported a relationship between PSA kinetics and DR of PET/CT. Pooled DR of radiolabelled choline PET/CT increased to 65% (95% CI 58-71) when PSAdt was ≤6 months and to 71% (95% CI 66-76) and 77% (95% CI 71-82) when PSAvel was >1 or >2 ng/(mL year), respectively. PSAdt ≤6 months and PSAvel >1 or >2 ng/(mL year) proved to be relevant factors in predicting the positive result of radiolabelled choline PET/CT. CONCLUSIONS: Due to the strong relationship between PSA kinetics and DR of radiolabelled choline PET/CT, beyond PSA values, PSAdt and PSAvel should be taken into account in the selection of PCa patients who should undergo radiolabelled choline PET/CT for restaging.

Does FDG PET-Based Radiomics Have an Added Value for Prediction of Overall Survival in Non-Small Cell Lung Cancer?

Objectives: Radiomics and machine learning are innovative approaches to improve the clinical management of NSCLC. However, there is less information about the additive value of FDG PET-based radiomics compared with clinical and imaging variables. Methods: This retrospective study included 320 NSCLC patients who underwent PET/CT with FDG at initial staging. VOIs were placed on primary tumors only. We included a total of 94 variables, including 87 textural features extracted from PET studies, SUVmax, MTV, TLG, TNM stage, histology, age, and gender. We used the least absolute shrinkage and selection operator (LASSO) regression to select variables with the highest predictive value. Although several radiomics variables are available, the added value of these predictors compared with clinical and imaging variables is still under evaluation. Three hundred and twenty NSCLC patients were included in this retrospective study and underwent 18F-FDG PET/CT at initial staging. In this study, we evaluated 94 variables, including 87 textural features, SUVmax, MTV, TLG, TNM stage, histology, age, and gender. Image-based predictors were extracted from a volume of interest (VOI) positioned on the primary tumor. The least absolute shrinkage and selection operator (LASSO) Cox regression was used to reduce the number of variables and select only those with the highest predictive value. The predictive model implemented with the variables selected using the LASSO analysis was compared with a reference model using only a tumor stage and SUVmax. Results: NGTDM coarseness, SUVmax, and TNM stage survived the LASSO analysis and were used for the radiomic model. The AUCs obtained from the reference and radiomic models were 80.82 (95%CI, 69.01-92.63) and 81.02 (95%CI, 69.07-92.97), respectively (p = 0.98). The median OS in the reference model was 17.0 months in high-risk patients (95%CI, 11-21) and 113 months in low-risk patients (HR 7.47, p < 0.001). In the radiomic model, the median OS was 16.5 months (95%CI, 11-20) and 113 months in high- and low-risk groups, respectively (HR 9.64, p < 0.001). Conclusions: Our results indicate that a radiomic model composed using the tumor stage, SUVmax, and a selected radiomic feature (NGTDM_Coarseness) predicts survival in NSCLC patients similarly to a reference model composed only by the tumor stage and SUVmax. Replication of these preliminary results is necessary.

Weighted registration of 123I-FP-CIT SPECT images improves accuracy of binding potential estimates in pathologically low striatal uptake.

To test whether the use of a striatum weighted image may improve registration accuracy and diagnostic outcome in patients with parkinsonian syndromes (PS), weighted images were generated by increasing signal intensity of striatal voxels and used as intermediate dataset for co-registering the brain image onto template. Experimental validation was performed using an anthropomorphic striatal phantom. (123)I-FP-CIT SPECT binding ratios were manually determined in 67 PS subjects and compared to those obtained using unsupervised standard (UWR) and weighted registered (WR) approach. Normalized cost function was used to evaluate the accuracy of phantom and subjects registered images to the template. Reproducibility between unsupervised and manual ratios was assessed by using intra-class correlation coefficient (ICC) and Bland and Altman analysis. Correlation coefficient was used to assess the dependence of semi-quantitative ratios on clinical findings. Weighted method improves accuracy of brain registration onto template as determined by cost function in phantom (0.86 ± 0.06 vs. 0.98 ± 0.02; Student's t-test, P = 0.04) and in subject scans (0.69 ± 0.06 vs. 0.53 ± 0.06; Student's t-test, P < 0.0001). Agreement between manual and unsupervised derived binding ratios as measured by ICC was significantly higher on WR as compared to UWR images (0.91 vs. 0.76). Motor UPDRS score was significantly correlated with manual and unsupervised derived binding potential. In phantom, as well as in subjects studies, correlations were more significant using the WR method (BPm: R(2) = 0.36, P = 0.0001; BPwr: R(2) = 0.368, P = 0.0001; BPuwr: R(2) = 0.300, P = 0.0008). Weighted registration improves accuracy of binding potential estimates and may be a promising approach to enhance the diagnostic outcome of SPECT imaging, correlation with disease severity, and for monitoring disease progression in Parkinsonian syndromes.

[11C]choline positron emission tomography/computerized tomography for early detection of prostate cancer recurrence in patients with low increasing prostate specific antigen.

PURPOSE: The effectiveness of salvage therapy in prostate cancer is greater for low prostate specific antigen values. Therefore, early detection of tumor recurrence is warranted. [(11)C]choline positron emission tomography/computerized tomography has the potential of early restaging of prostate cancer with low prostate specific antigen, but the selection of patients at high risk for positive [(11)C]choline positron emission tomography/computerized tomography is desirable to optimize salvage therapy. MATERIALS AND METHODS: This retrospective study included 75 patients with prostate cancer with an increasing prostate specific antigen less than 1.5 ng/ml after radical prostatectomy who never received antiandrogen deprivation therapy or salvage radiotherapy who underwent [(11)C]choline positron emission tomography/computerized tomography for the restaging of disease. Binary logistic regression was used to assess predictive factors of positive [(11)C]choline positron emission tomography/computerized tomography. Included variables were trigger prostate specific antigen, prostate specific antigen doubling time, age, pathological stage and Gleason score. RESULTS: Median prostate specific antigen was 0.61 ng/ml. [(11)C]choline positron emission tomography/computerized tomography was positive in 16 of 75 patients (21%). On univariate analysis prostate specific antigen doubling time less than 6 months was the only factor significantly associated with an increased risk of positive [(11)C]choline positron emission tomography/computerized tomography (OR 7.77, 95% CI 2.34-25.80, p = 0.001). In patients with prostate specific antigen doubling time less than 6 months, the positive detection rate of [(11)C]choline positron emission tomography/computerized tomography increased to 50%. CONCLUSIONS: In patients with prostate cancer with biochemical failure after radical prostatectomy and prostate specific antigen less than 1.5 ng/ml, prostate specific antigen doubling time less than 6 months predicts positive [(11)C]choline positron emission tomography/computerized tomography. In these patients [(11)C]choline positron emission tomography/computerized tomography may reduce by 50% the number in whom salvage therapy is initiated empirically without knowing the disease location.

Microalbuminuria predicts silent myocardial ischaemia in type 2 diabetes patients.

PURPOSE: Myocardial ischaemia is frequently silent in patients with type 2 diabetes. Although it has been proposed as a potential screening tool, the role of myocardial perfusion single photon emission computed tomography (MPS) has recently been questioned, due to the low prevalence of positive scans and the low rate of cardiac events. The aim of this study was to assess if pretest clinical variables can identify a subgroup of asymptomatic patients with type 2 diabetes at risk of silent myocardial ischaemia and a subsequent poor outcome METHODS: This prospective study included 77 patients (50 men, mean age 63 ± 9 years) with type 2 diabetes and no known coronary artery disease (CAD) or angina pectoris who underwent gated MPS to screen for CAD between March 2006 and October 2008. MPS images were interpreted using a semiquantitative visual 20-segment model to define summed stress, rest and difference scores. Ischaemia was defined as a sum difference score (SDS) ≥2. Patients were followed-up (median 4.1 years, range 0.8 - 6.1 years) and cardiac hard events (cardiac death or nonfatal myocardial infarction) were recorded. RESULTS: Silent ischaemia was detected in 25 of the 77 patients (32 %). Specifically, 10 patients (13 %) had mild ischaemia (SDS 2 to ≤4) and 15 patients (19 %) had severe ischaemia (SDS >4). In univariate binary logistic analysis, microalbuminuria was the only significant predictor of silent ischaemia on MPS (odds ratio 4.42, 95 % CI 1.27 - 15.40; P = 0.019). The overall accuracy of microalbuminuria for predicting silent ischaemia was 71.4 % and was 89.6 % for predicting severe ischaemia. Kaplan-Meier curves showed no significant group differences in 5-year cardiac event-free survival between patients with and those without microalbuminuria, or between patients with SDS ≥2 and those with SDS <2. In contrast, 5-year event-free survival was significantly lower in patients with SDS >4 than in patients with SDS ≤4: 55.6 % (95 % CI 39.0 - 72.2 %) vs. 94.5 % (95 % CI: 91.4 - 97.6 %), respectively (Breslow test, chi-square 20.9, P < 0.001). Median cardiac event-free survival was not observed in the whole group, while the 25th percentile of cardiac event-free survival was reached only in patients with SDS >4 (2.3 years). In univariate Cox regression analysis, SDS >4 predicted cardiac event-free survival (hazard ratio 12.87, 95 % CI 2.86 - 27.98; P = 0.001), while SDS ≥2 did not (hazard ratio 2.78, 95 % CI 0.62 - 12.46, P = 0.16). CONCLUSION: In this group of patients with type 2 diabetes, microalbuminuria was the only predictor of silent ischaemia on MPS. Assessment of microalbuminuria should be routinely considered among the first risk stratification steps for CAD in patients with type 2 diabetes, even though severe ischaemia on MPS is a major predictor of cardiac event-free survival.

Assessment of Response to Immunotherapy in Patients with Hodgkin Lymphoma: Towards Quantifying Changes in Tumor Burden Using FDG-PET/CT.

Immune checkpoint inhibitors are currently the standard of care for many advanced solid tumors, and they have been recently approved for the treatment of relapsed/refractory Hodgkin lymphoma and primary mediastinal B cell lymphoma. Assessments of the response to immunotherapy may be complicated by the occurrence of the flare/pseudoprogression phenomenon, consisting of initial tumor enlargement and even the appearance of new lesions, followed by a response, which may initially be indistinguishable from true progression. There have been efforts to characterize and capture the new patterns of response observed during immunotherapy, namely, pseudoprogression and delayed response, and several immune-related response criteria have been proposed. Confirming progression on a subsequent scan and measuring the total tumor burden are both common in immune-related criteria. Due to the peculiarity of hematologic malignancies, lymphoma-specific immune-related criteria have been developed (LYRIC), and they have been evaluated in research studies in comparison to the Lugano Classification. In this review work, we illustrate the evolution of the response criteria in lymphomas from the first CT-based criteria to the development of the PET-based Lugano Classification, further refined to take into account the flare phenomenon encountered during immunotherapy. We also describe the additional contribution of PET-derived volumetric parameters to the interpretation of responses during immunotherapy.

Machine Learning Model to Predict Diagnosis of Mild Cognitive Impairment by Using Radiomic and Amyloid Brain PET.

PURPOSE: The study aimed to develop a deep learning model for predicting amnestic mild cognitive impairment (aMCI) diagnosis using radiomic features and amyloid brain PET. PATIENTS AND METHODS: Subjects (n = 328) from the Alzheimer's Disease Neuroimaging Initiative database and the EudraCT 2015-001184-39 trial (159 males, 169 females), with a mean age of 72 ± 7.4 years, underwent PET/CT with 18 F-florbetaben. The study cohort consisted of normal controls (n = 149) and subjects with aMCI (n = 179). Thirteen gray-level run-length matrix radiomic features and amyloid loads were extracted from 27 cortical brain areas. The least absolute shrinkage and selection operator regression was used to select features with the highest predictive value. A feed-forward neural multilayer network was trained, validated, and tested on 70%, 15%, and 15% of the sample, respectively. Accuracy, precision, F1-score, and area under the curve were used to assess model performance. SUV performance in predicting the diagnosis of aMCI was also assessed and compared with that obtained from the machine learning model. RESULTS: The machine learning model achieved an area under the receiver operating characteristic curve of 90% (95% confidence interval, 89.4-90.4) on the test set, with 80% and 78% for accuracy and F1-score, respectively. The deep learning model outperformed SUV performance (area under the curve, 71%; 95% confidence interval, 69.7-71.4; 57% accuracy, 48% F1-score). CONCLUSIONS: Using radiomic and amyloid PET load, the machine learning model identified MCI subjects with 84% specificity at 81% sensitivity. These findings show that a deep learning algorithm based on radiomic data and amyloid load obtained from brain PET images improves the prediction of MCI diagnosis compared with SUV alone.

Multivariable Risk Modelling and Survival Analysis with Machine Learning in SARS-CoV-2 Infection.

AIM: To evaluate the performance of a machine learning model based on demographic variables, blood tests, pre-existing comorbidities, and computed tomography(CT)-based radiomic features to predict critical outcome in patients with acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We retrospectively enrolled 694 SARS-CoV-2-positive patients. Clinical and demographic data were extracted from clinical records. Radiomic data were extracted from CT. Patients were randomized to the training (80%, n = 556) or test (20%, n = 138) dataset. The training set was used to define the association between severity of disease and comorbidities, laboratory tests, demographic, and CT-based radiomic variables, and to implement a risk-prediction model. The model was evaluated using the C statistic and Brier scores. The test set was used to assess model prediction performance. RESULTS: Patients who died (n = 157) were predominantly male (66%) over the age of 50 with median (range) C-reactive protein (CRP) = 5 [1, 37] mg/dL, lactate dehydrogenase (LDH) = 494 [141, 3631] U/I, and D-dimer = 6.006 [168, 152.015] ng/mL. Surviving patients (n = 537) had median (range) CRP = 3 [0, 27] mg/dL, LDH = 484 [78, 3.745] U/I, and D-dimer = 1.133 [96, 55.660] ng/mL. The strongest risk factors were D-dimer, age, and cardiovascular disease. The model implemented using the variables identified using the LASSO Cox regression analysis classified 90% of non-survivors as high-risk individuals in the testing dataset. In this sample, the estimated median survival in the high-risk group was 9 days (95% CI; 9-37), while the low-risk group did not reach the median survival of 50% (p < 0.001). CONCLUSIONS: A machine learning model based on combined data available on the first days of hospitalization (demographics, CT-radiomics, comorbidities, and blood biomarkers), can identify SARS-CoV-2 patients at risk of serious illness and death.

[11C]Choline PET/CT detection of bone metastases in patients with PSA progression after primary treatment for prostate cancer: comparison with bone scintigraphy.

PURPOSE: The aim of this study was to evaluate the clinical usefulness of [(11)C]choline positron emission tomography (PET)/CT in comparison with bone scintigraphy (BS) in detecting bone metastases (BM) of patients with biochemical progression after radical treatment for prostate cancer (PCa). METHODS: Seventy-eight consecutive patients with biochemical progression of PCa (mean prostate-specific antigen 21.1 ng/ml, range 0.2-500.0 ng/ml) referred for both [(11)C]choline PET/CT and BS for restaging purposes were retrospectively analysed. The diagnostic accuracy of [(11)C]choline PET/CT and BS was assessed by using morphological imaging and/or follow-up as standards of reference. As equivocal findings were found, the accuracy analysis was performed twice, once including them as positive and once as negative. A separate analysis was also performed in hormone-resistant patients and data compared with those of patients who did not receive anti-androgenic treatment. RESULTS: Equivocal findings occurred in 1 of 78 (1%) cases in [(11)C]choline PET/CT and in 21 of 78 (27%) cases in BS. Depending on their attribution as either positive or negative, the ranges of sensitivity, specificity, positive predictive value, negative predictive value and accuracy for [(11)C]choline PET/CT were 89-89%, 98-100%, 96-100%, 94-96% and 95-96%, respectively. For BS they were 100-70%, 75-100%, 68--100%, 100-86% and 83-90%, respectively. Concordant findings between [(11)C]choline PET/CT and BS occurred in 55 of 78 (71%) cases. The accuracy of [(11)C]choline PET/CT did not significantly (p = 0.30) differ between hormone-resistant patients (97%) and those who did not receive anti-androgenic treatment (95%). CONCLUSION: In clinical practice, [(11)C]choline PET/CT may not replace BS because of its lower sensitivity. However, for its high specificity, [(11)C]choline PET/CT positive findings may accurately predict the presence of BM. Equivocal findings are more frequent in BS than [(11)C]choline PET/CT.

18F-FDG PET uptake in the pre-Huntington disease caudate affects the time-to-onset independently of CAG expansion size.

PURPOSE: To test in a longitudinal follow-up study whether basal glucose metabolism in subjects with a genetic risk of Huntington disease (HD) may influence the onset of manifest symptoms. METHODS: The study group comprised 43 presymptomatic (preHD) subjects carrying the HD mutation. They underwent a (18)F-FDG PET scan and were prospectively followed-up for at least 5 years using the unified HD rating scale to detect clinical changes. Multiple regression analysis included subject's age, CAG mutation size and glucose uptake as variables in a model to predict age at onset. RESULTS: Of the 43 preHD subjects who manifested motor symptoms, suggestive of HD, after 5 years from the PET scan, 26 showed a mean brain glucose uptake below the cut-off of 1.0493 in the caudate, significantly lower than the 17 preHD subjects who remained symptom-free (P < 0.0001). This difference was independent of mutation size. Measurement of brain glucose uptake improved the CAG repeat number and age-based model for predicting age at onset by 37 %. CONCLUSION: A reduced level of glucose metabolism in the brain caudate may represent a predisposing factor that contributes to the age at onset of HD in preHD subjects, in addition to the mutation size.

Methodological Aspects and the Prognostic Value of Metabolic Tumor Volume assessed with 18F-FDG PET/CT in Lymphomas.

Although metabolic tumor volume (MTV) assessed with pretreatment 18F-FDG PET/CT has shown significant prognostic value across many lymphoma types, it is still not used in clinical practice due to technical concerns and the lack of standardisation. Numerous studies on the prognostic value of MTV in lymphomas have been published in recent years, but there is still no full agreement on the best methodology for MTV calculation. In this paper, we reviewed the methodological aspects of MTV assessment and reported recent works about its impact on outcome in lymphomas, with a focus on Hodgkin lymphoma (HL) and diffuse large B cell lymphoma (DLBCL).

PET translates neurophysiology into images: A review to stimulate a network between neuroimaging and basic research.

In the last decades there has been a progressive advance in the development of techniques able to explore in humans neurophysiologic and neurochemical processes. Positron emission tomography (PET) is a very powerful technique allowing to study a quite variable range of physiological and biochemical processes in the healthy subjects and in diseases. Apart from its capacity to provide pathophysiological information, PET is also important for the objective assessment of therapeutic efficacy. Initial studies were performed measuring cerebral metabolic rate for glucose (CMRglc) and cerebral blood flow (CBF), representing an indirect index of synaptic activity. The advent of receptor tracers allowed measuring other important physiological parameters, such as receptor occupancy, and endogenous release. In neuropsychiatric disorders, as Alzheimer disease, schizophrenia, epilepsy and Huntington disease, PET has been useful to elaborate hypothesis of the pathogenesis, to relate symptoms to biological variables and to study individuals at increased risk. The new concepts of neurovascular unit and default network, preferentially active at rest, can significantly change the approach of PET, with images reflecting a complex scenario, not merely limited to neural activity, but involving the activity of the entire neurovascular unit and the multifunctional role of astrocytes. To detect dysfunction of the dialog between glutamatergic neurons and astrocytes could lead to a better understanding of altered functional brain images. In this direction a professional network between PET researchers and basic scientists, could give a determinant improvement in the capability to understand the complex physiological and pathophysiological cerebral world.