Ventricular tachycardia ablation guided or aided by scar characterization with cardiac magnetic resonance: rationale and design of VOYAGE study.

BACKGROUND: Radiofrequency ablation has been shown to be a safe and effective treatment for scar-related ventricular arrhythmias (VA). Recent preliminary studies have shown that real time integration of late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) images with electroanatomical map (EAM) data may lead to increased procedure efficacy, efficiency, and safety. METHODS: VOYAGE is a prospective, randomized, multicenter controlled open label study designed to compare in terms of efficacy, efficiency, and safety a CMR aided/guided workflow to standard EAM-guided ventricular tachycardia (VT) ablation. Patients with an ICD or with ICD implantation expected within 1 month, with scar related VT, suitable for CMR and multidetector computed tomography (MDCT) will be randomized to a CMR-guided or CMR-aided approach, whereas subjects unsuitable for imaging or with image quality deemed not sufficient for postprocessing will be allocated to standard of care ablation. Primary endpoint is defined as VT recurrences (sustained or requiring appropriate ICD intervention) during 12 months follow-up, excluding the first month of blanking period. Secondary endpoints will include procedural efficiency, safety, impact on quality of life and comparison between CMR-guided and CMR-aided approaches. Patients will be evaluated at 1, 6 and 12 months. DISCUSSION: The clinical impact of real time CMR-guided/aided ablation approaches has not been thoroughly assessed yet. This study aims at defining whether such workflow results in more effective, efficient, and safer procedures. If proven to be of benefit, results from this study could be applied in large scale interventional practice. Trial registrationClinicalTrials.gov, NCT04694079, registered on January 1, 2021.

Low-dose CT for lung cancer screening: position paper from the Italian college of thoracic radiology.

Smoking is the main risk factor for lung cancer (LC), which is the leading cause of cancer-related death worldwide. Independent randomized controlled trials, governmental and inter-governmental task forces, and meta-analyses established that LC screening (LCS) with chest low dose computed tomography (LDCT) decreases the mortality of LC in smokers and former smokers, compared to no-screening, especially in women. Accordingly, several Italian initiatives are offering LCS by LDCT and smoking cessation to about 10,000 high-risk subjects, supported by Private or Public Health Institutions, envisaging a possible population-based screening program. Because LDCT is the backbone of LCS, Italian radiologists with LCS expertise are presenting this position paper that encompasses recommendations for LDCT scan protocol and its reading. Moreover, fundamentals for classification of lung nodules and other findings at LDCT test are detailed along with international guidelines, from the European Society of Thoracic Imaging, the British Thoracic Society, and the American College of Radiology, for their reporting and management in LCS. The Italian College of Thoracic Radiologists produced this document to provide the basics for radiologists who plan to set up or to be involved in LCS, thus fostering homogenous evidence-based approach to the LDCT test over the Italian territory and warrant comparison and analyses throughout National and International practices.

T1 and T2 mapping in the identification of acute myocardial injury in patients with NSTEMI.

AIMS: To test T1 and T2 mapping in the assessment of acute myocardial injury in patients with non-ST-segment elevation myocardial infarction (NSTEMI), evaluated before revascularization. METHODS: Forty-seven patients with acute NSTEMI underwent cardiac magnetic resonance (CMR) at 1.5 T, including T1 and T2 mapping. RESULTS: Coronary angiography (CA) evidenced an obstructive coronary artery disease (CAD) in 36 patients (80%) and a non-obstructive CAD in 11 patients (20%). Edema was detected in 51.1/65.9% of patients in T1/T2 maps, respectively. This difference was due to artifacts in T1 maps. T1/T2 values were significantly higher in the infarcted myocardium (IM) compared with the remote myocardium (RM) (in T1: 1151.6 ± 53.5 ms vs. 958.2 ± 38.6 ms, respectively; in T2: 69 ± 6 ms vs. 51.9 ± 2.9 ms, respectively; p < 0.0001 for both). We found both an obstructive CAD at CA and myocardial edema at CMR in 53.2% of patients, while 8.5% of patients had a non-obstructive CAD and no edema. However, 25.5% of patients had an obstructive CAD without edema, while 12.8% of patients showed edema despite a non-obstructive CAD. Furthermore, in 6 of the edema-positive patients with multi-vessels obstructive CAD, CMR identified myocardial edema in a vascular territory different from that of the lesion supposed to be the culprit at CA. CONCLUSIONS: In a non-negligible percentage of NSTEMI patients, T1 and T2 mapping detect myocardial edema without significant stenosis at CA and vice versa. Therefore, CA and CMR edema imaging might provide complementary information in the evaluation of NSTEMI.

Progression of brain atrophy in the early stages of Parkinson's disease: a longitudinal tensor-based morphometry study in de novo patients without cognitive impairment.

The presence of brain atrophy and its progression in early Parkinson's disease (PD) are still a matter of debate, particularly in patients without cognitive impairment. The aim of this longitudinal study was to assess whether PD patients who remain cognitively intact develop progressive atrophic changes in the early stages of the disease. For this purpose, we employed high-resolution T1-weighted MR imaging to compare 22 drug-naïve de novo PD patients without cognitive impairment to 17 age-matched control subjects, both at baseline and at three-year follow-up. We used tensor-based morphometry to explore the presence of atrophic changes at baseline and to compute yearly atrophy rates, after which we performed voxel-wise group comparisons using threshold-free cluster enhancement. At baseline, we did not observe significant differences in regional atrophy in PD patients with respect to control subjects. In contrast, PD patients showed significantly higher yearly atrophy rates in the prefrontal cortex, anterior cingulum, caudate nucleus, and thalamus when compared to control subjects. Our results indicate that even cognitively preserved PD patients show progressive cortical and subcortical atrophic changes in regions related to cognitive functions and that these changes are already detectable in the early stages of the disease.

The burden of microstructural damage modulates cortical activation in elderly subjects with MCI and leuko-araiosis. A DTI and fMRI study.

The term leuko-araiosis (LA) describes a common chronic affection of the cerebral white matter (WM) in the elderly due to small vessel disease with variable clinical correlates. To explore whether severity of LA entails some adaptive reorganization in the cerebral cortex we evaluated with functional MRI (fMRI) the cortical activation pattern during a simple motor task in 60 subjects with mild cognitive impairment and moderate or severe (moderate-to-severe LA group, n = 46) and mild (mild LA group, n = 14) LA extension on visual rating. The microstructural damage associated with LA was measured on diffusion tensor data by computation of the mean diffusivity (MD) of the cerebral WM and by applying tract based spatial statistics (TBSS). Subjects were examined with fMRI during continuous tapping of the right dominant hand with task performance measurement. Moderate-to-severe LA group showed hyperactivation of left primary sensorimotor cortex (SM1) and right cerebellum. Regression analyses using the individual median of WM MD as explanatory variable revealed a posterior shift of activation within the left SM1 and hyperactivation of the left SMA and paracentral lobule and of the bilateral cerebellar crus. These data indicate that brain activation is modulated by increasing severity of LA with a local remapping within the SM1 and increased activity in ipsilateral nonprimary sensorimotor cortex and bilateral cerebellum. These potentially adaptive changes as well lack of contralateral cerebral hemisphere hyperactivation are in line with sparing of the U fibers and brainstem and cerebellar WM tracts and the emerging microstructual damage of the corpus callosum revealed by TBSS with increasing severity of LA.

Efficacy of MRI data harmonization in the age of machine learning: a multicenter study across 36 datasets.

Pooling publicly-available MRI data from multiple sites allows to assemble extensive groups of subjects, increase statistical power, and promote data reuse with machine learning techniques. The harmonization of multicenter data is necessary to reduce the confounding effect associated with non-biological sources of variability in the data. However, when applied to the entire dataset before machine learning, the harmonization leads to data leakage, because information outside the training set may affect model building, and potentially falsely overestimate performance. We propose a 1) measurement of the efficacy of data harmonization; 2) harmonizer transformer, i.e., an implementation of the ComBat harmonization allowing its encapsulation among the preprocessing steps of a machine learning pipeline, avoiding data leakage by design. We tested these tools using brain T1-weighted MRI data from 1740 healthy subjects acquired at 36 sites. After harmonization, the site effect was removed or reduced, and we showed the data leakage effect in predicting individual age from MRI data, highlighting that introducing the harmonizer transformer into a machine learning pipeline allows for avoiding data leakage by design.

Test-retest repeatability of myocardial radiomic features from quantitative cardiac magnetic resonance T1 and T2 mapping.

Radiomics of cardiac magnetic resonance (MR) imaging has proved to be potentially useful in the study of various myocardial diseases. Therefore, assessing the repeatability degree in radiomic features measurement is of fundamental importance. The aim of this study was to assess test-retest repeatability of myocardial radiomic features extracted from quantitative T1 and T2 maps. A representative group of 24 subjects (mean age 54 ±â€¯18 years) referred for clinical cardiac MR imaging were enrolled in the study. For each subject, T1 and T2 mapping through MOLLI and T2-prepared TrueFISP acquisition sequences, respectively, were performed at 1.5 T. Then, 98 radiomic features of different classes (shape, first-order, second-order) were extracted from a region of interest encompassing the whole left ventricle myocardium in a short axis slice. The repeatability was assessed performing different and complementary analyses: intraclass correlation coefficient (ICC) and limits of agreement (LOA) (i.e., the interval within which 95% of the percentage differences between two repeated measures are expected to lie). Radiomic features were characterized by a relatively wide range of repeatability degree in terms of both ICC and LOA. Overall, 44.9% and 38.8% of radiomic features showed ICC values >0.75 for T1 and T2 maps, respectively, while 25.5% and 23.4% of radiomic features showed LOA between ±10%. A subset of radiomic features for T1 (Mean, Median, 10Percentile, 90Percentile, RootMeanSquared, Imc2, RunLengthNonUniformityNormalized, RunPercentage and ShortRunEmphasis) and T2 (MaximumDiameter, RunLengthNonUniformityNormalized, RunPercentage, ShortRunEmphasis) maps presented both ICC > 0.75 and LOA between ±5%. Overall, radiomic features extracted from T1 maps showed better repeatability performance than those extracted from T2 maps, with shape features characterized by better repeatability than first-order and textural features. Moreover, only a limited subset of 9 and 4 radiomic features for T1 and T2 maps, respectively, showed high repeatability degree in terms of both ICC and LOA. These results confirm the importance of assessing test-retest repeatability degree in radiomic feature estimation and might be useful for a more effective/reliable use of myocardial T1 and T2 mapping radiomics in clinical or research studies.

Collinearity and Dimensionality Reduction in Radiomics: Effect of Preprocessing Parameters in Hypertrophic Cardiomyopathy Magnetic Resonance T1 and T2 Mapping.

Radiomics and artificial intelligence have the potential to become a valuable tool in clinical applications. Frequently, radiomic analyses through machine learning methods present issues caused by high dimensionality and multicollinearity, and redundant radiomic features are usually removed based on correlation analysis. We assessed the effect of preprocessing-in terms of voxel size resampling, discretization, and filtering-on correlation-based dimensionality reduction in radiomic features from cardiac T1 and T2 maps of patients with hypertrophic cardiomyopathy. For different combinations of preprocessing parameters, we performed a dimensionality reduction of radiomic features based on either Pearson's or Spearman's correlation coefficient, followed by the computation of the stability index. With varying resampling voxel size and discretization bin width, for both T1 and T2 maps, Pearson's and Spearman's dimensionality reduction produced a slightly different percentage of remaining radiomic features, with a relatively high stability index. For different filters, the remaining features' stability was instead relatively low. Overall, the percentage of eliminated radiomic features through correlation-based dimensionality reduction was more dependent on resampling voxel size and discretization bin width for textural features than for shape or first-order features. Notably, correlation-based dimensionality reduction was less sensitive to preprocessing when considering radiomic features from T2 compared with T1 maps.

Neurodegeneration in friedreich's ataxia is associated with a mixed activation pattern of the brain. A fMRI study.

Friedreich's ataxia (FRDA) is associated with a distributed pattern of neurodegeneration in the spinal cord and the brain secondary to selective neuronal loss. We used functional MR Imaging (fMRI) to explore brain activation in FRDA patients during two motor-sensory tasks of different complexity, i.e. continuous hand tapping and writing of "8" figure, with the right dominant hand and without visual feedback. Seventeen FRDA patients and two groups of age-matched healthy controls were recruited. Task execution was monitored and recorded using MR-compatible devices. Hand tapping was correctly performed by 11 (65%) patients and writing of the "8" by 7 (41%) patients. After correction for behavioral variables, FRDA patients showed in both tasks areas of significantly lower activation in the left primary sensory-motor cortex and right cerebellum. Also left thalamus and right dorsolateral prefrontal cortex showed hypo-activation during hand tapping. During writing of the "8" task FRDA patients showed areas of higher activation in the right parietal and precentral cortex, globus pallidus, and putamen. Activation of right parietal cortex, anterior cingulum, globus pallidus, and putamen during writing of the "8" increased with severity of the neurological deficit. In conclusion fMRI demonstrates in FRDA a mixed pattern constituted by areas of decreased activation and areas of increased activation. The decreased activation in the primary motor cortex and cerebellum presumably reflects a regional neuronal damage, the decreased activation of the left thalamus and primary sensory cortex could be secondary to deafferentation phenomena, and the increased activation of right parietal cortex and striatum might have a possible compensatory significance.

Hypoactivation of the primary sensorimotor cortex in de novo Parkinson's disease : a motor fMRI study under controlled conditions.

INTRODUCTION: Nuclear medicine studies in Parkinson's disease (PD) indicate that nigrostriatal damage causes a widespread cortical hypoactivity assumed to be due to reduced excitatory thalamic outflow. However, so far, functional MRI (fMRI) studies have provided controversial data about this "functional deafferentation" phenomenon. To further clarify this issue, we assessed, with fMRI, de novo drug-naive PD patients using a relatively complex motor task under strictly controlled conditions. METHODS: Nineteen de novo PD patients with right-predominant or bilateral symptoms and 13 age-matched healthy volunteers performed continuous writing of "8" figures with the right-dominant hand using a MR-compatible device that enables identification of incorrectly performed tasks and measures the size and the frequency of the "8"s. The data were analyzed with FSL software and correlated with the clinical severity rated according to the Hoehn and Yahr (HY) staging system. RESULTS: Fifteen (89%) of 19 PD patients and 12 (92%) of 13 controls correctly executed the task. PD patients showed significant hypoactivation of the left primary sensorimotor cortex (SM1) and cerebellum and no hyperactive areas as compared to controls. However, activation in SM1 and supplementary motor area bilaterally, in left supramarginal, parietal inferior, parietal superior and frontal superior gyri as well as in right parietal superior and angular gyri paralleled increasing disease severity as assessed with the HY stage. CONCLUSIONS: In line with the "deafferentation hypothesis", fMRI demonstrates hypoactivation of the SM1 in the early clinical stage of PD.

Image resampling and discretization effect on the estimate of myocardial radiomic features from T1 and T2 mapping in hypertrophic cardiomyopathy.

Radiomics is emerging as a promising and useful tool in cardiac magnetic resonance (CMR) imaging applications. Accordingly, the purpose of this study was to investigate, for the first time, the effect of image resampling/discretization and filtering on radiomic features estimation from quantitative CMR T1 and T2 mapping. Specifically, T1 and T2 maps of 26 patients with hypertrophic cardiomyopathy (HCM) were used to estimate 98 radiomic features for 7 different resampling voxel sizes (at fixed bin width), 9 different bin widths (at fixed resampling voxel size), and 7 different spatial filters (at fixed resampling voxel size/bin width). While we found a remarkable dependence of myocardial radiomic features from T1 and T2 mapping on image filters, many radiomic features showed a limited sensitivity to resampling voxel size/bin width, in terms of intraclass correlation coefficient (> 0.75) and coefficient of variation (< 30%). The estimate of most textural radiomic features showed a linear significant (p < 0.05) correlation with resampling voxel size/bin width. Overall, radiomic features from T2 maps have proven to be less sensitive to image preprocessing than those from T1 maps, especially when varying bin width. Our results might corroborate the potential of radiomics from T1/T2 mapping in HCM and hopefully in other myocardial diseases.

Case Series: Recovery of Chemotherapy-Related Acute Heart Failure by the Combined Use of Sacubitril Valsartan and Wearable Cardioverter Defibrillator: A Novel Winning Combination in Cardio-Oncology.

Effective anticancer treatments have dramatically improved the outcome of patients with cancer, but cardiac toxicity reduces their clinical efficacy in a non-negligible percentage of patients. Sacubitril/valsartan is a new paradigm in the treatment of chronic heart failure, with a reduced ejection fraction due to the enhancement of natriuretic peptides' properties when coupled with a blocking effect on the angiotensin II type 1 (AT1) receptors. As with other clinical conditions of heart failure with potentially reversible declines in cardiac function, a wearable cardioverter defibrillator (WCD) is a valid tool for protection against sudden death until recovery occurs. We report a case series of four patients with chemotherapy-related acute cardiac failure with severely reduced cardiac function. They were successfully treated with sacubitril/valsartan while being protected from malignant arrhythmias using a wearable cardioverter defibrillator until the recovery of cardiac function. Sacubitril/valsartan was confirmed to be effective in anthracycline-related cardiac toxicity and the wearable cardioverter defibrillator should be considered as a support tool even in the oncology patient.

Effect of data leakage in brain MRI classification using 2D convolutional neural networks.

In recent years, 2D convolutional neural networks (CNNs) have been extensively used to diagnose neurological diseases from magnetic resonance imaging (MRI) data due to their potential to discern subtle and intricate patterns. Despite the high performances reported in numerous studies, developing CNN models with good generalization abilities is still a challenging task due to possible data leakage introduced during cross-validation (CV). In this study, we quantitatively assessed the effect of a data leakage caused by 3D MRI data splitting based on a 2D slice-level using three 2D CNN models to classify patients with Alzheimer's disease (AD) and Parkinson's disease (PD). Our experiments showed that slice-level CV erroneously boosted the average slice level accuracy on the test set by 30% on Open Access Series of Imaging Studies (OASIS), 29% on Alzheimer's Disease Neuroimaging Initiative (ADNI), 48% on Parkinson's Progression Markers Initiative (PPMI) and 55% on a local de-novo PD Versilia dataset. Further tests on a randomly labeled OASIS-derived dataset produced about 96% of (erroneous) accuracy (slice-level split) and 50% accuracy (subject-level split), as expected from a randomized experiment. Overall, the extent of the effect of an erroneous slice-based CV is severe, especially for small datasets.

Effect of echo spacing and readout bandwidth on basic performances of EPI-fMRI acquisition sequences implemented on two 1.5 T MR scanner systems.

PURPOSE: Although in EPI-fMRI analyses typical acquisition parameters (TR, TE, matrix, slice thickness, etc.) are generally employed, various readout bandwidth (BW) values are used as a function of gradients characteristics of the MR scanner. Echo spacing (ES) is another fundamental parameter of EPI-fMRI acquisition sequences but the employed ES value is not usually reported in fMRI studies. In the present work, the authors investigated the effect of ES and BW on basic performances of EPI-fMRI sequences in terms of temporal stability and overall image quality of time series acquisition. METHODS: EPI-fMRI acquisitions of the same water phantom were performed using two clinical MR scanner systems (scanners A and B) with different gradient characteristics and functional designs of radiofrequency coils. For both scanners, the employed ES values ranged from 0.75 to 1.33 ms. The used BW values ranged from 125.0 to 250.0 kHz/64pixels and from 78.1 to 185.2 kHz/64pixels for scanners A and B, respectively. The temporal stability of EPI-fMRI sequence was assessed measuring the signal-to-fluctuation noise ratio (SFNR) and signal drift (DR), while the overall image quality was assessed evaluating the signal-to-noise ratio (SNR(ts)) and nonuniformity (NU(ts)) of the time series acquisition. RESULTS: For both scanners, no significant effect of ES and BW on signal drift was revealed. The SFNR, NU(ts) and SNR(ts) values of scanner A did not significantly vary with ES. On the other hand, the SFNR, NU(ts), and SNR(ts) values of scanner B significantly varied with ES. SFNR (5.8%) and SNR(ts) (5.9%) increased with increasing ES. SFNR (25% scanner A, 32% scanner B) and SNR(ts) (26.2% scanner A, 30.1% scanner B) values of both scanners significantly decreased with increasing BW. NU(ts) values of scanners A and B were less than 3% for all BW and ES values. Nonetheless, scanner A was characterized by a significant upward trend (3% percentage of variation) of time series nonuniformity with increasing BW while NU(ts) of scanner B significantly increased (19% percentage of variation) with increasing ES. CONCLUSIONS: Temporal stability (SFNR and DR) and overall image quality (NU(ts) and SNR(ts)) of EPI-fMRI time series can significantly vary with echo spacing and readout bandwidth. The specific pattern of variation may depend on the performance of each single MR scanner system in terms of gradients characteristics, EPI sequence calibrations (eddy currents, shimming, etc.), and functional design of radiofrequency coil. Our results indicate that the employment of low BW improves not only the signal-to-noise ratio of EPI-fMRI time series but also the temporal stability of functional acquisitions. The use of minimum ES values is not entirely advantageous when the MR scanner system is characterized by gradients with low performances and suboptimal EPI sequence calibration. Since differences in basic performances of MR scanner system are potential source of variability for fMRI activation, phantom measurements of SFNR, DR, NU(ts), and SNR(ts) can be executed before subjects acquisitions to monitor the stability of MR scanner performances in clinical group comparison and longitudinal studies.

Characterization of Nyquist ghost in EPI-fMRI acquisition sequences implemented on two clinical 1.5 T MR scanner systems: effect of readout bandwidth and echo spacing.

In EPI-fMRI acquisitions, various readout bandwidth (BW) values are used as a function of gradients' characteristics of the MR scanner system. Echo spacing (ES) is another fundamental parameter of EPI-fMRI sequences, but the employed ES value is not usually reported in fMRI studies. Nyquist ghost is a typical EPI artifact that can degrade the overall quality of fMRI time series. In this work, the authors assessed the basic effect of BW and ES for two clinical 1.5 T MR scanner systems (scanner-A, scanner-B) on Nyquist ghost of gradient-echo EPI-fMRI sequences. BW range was: scanner-A, 1953-3906 Hz/pixel; scanner-B, 1220-2894 Hz/pixel. ES range was: scanner-A, scanner-B: 0.75-1.33 ms. The ghost-to-signal ratio of time series acquisition (GSRts) and drift of ghost-to-signal ratio (DRGSR) were measured in a water phantom. For both scanner-A (93% of variation) and scanner-B (102% of variation) the mean GSRts significantly increased with increasing BW. GSRts values of scanner-A did not significantly depended on ES. On the other hand, GSRts values of scanner-B significantly varied with ES, showing a downward trend (81% of variation) with increasing ES. In addition, a GSRts spike point at ES = 1.05 ms indicating a potential resonant effect was revealed. For both scanners, no significant effect of ES on DRGSR was revealed. DRGSR values of scanner-B did not significantly vary with BW, whereas DRGSR values of scanner-A significantly depended on BW showing an upward trend from negative to positive values with increasing BW. GSRts and DRGSR can significantly vary with BW and ES, and the specific pattern of variation may depend on gradients performances, EPI sequence calibrations and functional design of radiofrequency coil. Thus, each MR scanner system should be separately characterized. In general, the employment of low BW values seems to reduce the intensity and temporal variation of Nyquist ghost in EPI-fMRI time series. On the other hand, the use of minimum ES value might not be entirely advantageous when the MR scanner is characterized by gradients with low performances and suboptimal EPI sequence calibration.

Epidemiology and pathophysiologic insights of coronary atherosclerosis relevant for contemporary non-invasive imaging.

In the past few years significant changes have taken place in the diagnostic and therapeutic approach to patients with coronary artery disease (CAD) and/or ischemic heart disease (IHD). New discoveries about the development and progression of coronary atherosclerosis have changed the clinical landscape. At the same time a marked decrease in cardiovascular (CV) mortality and CAD incidence have been observed in many Countries but particularly in the most industrialized ones. This fall has been also observed in the incidence of stroke, sudden death, myocardial ischemia, myocardial infarction (MI), and prevalence of CAD. As a consequence, an increasing number of patients with chest pain exhibits non-significant stenosis at both invasive and non-invasive coronary angiography and the rate of coronary vessels revascularizations has greatly reduced. Coronary atherosclerosis and its characteristics have shown to be both diagnostic and therapeutic targets beyond obstructive CAD. The decreased prevalence of CAD in the general population has modified the pre-test probability (PTP) of disease. In this landscape the conventional stress imaging tests appear to have limited accuracy making the diagnosis of obstructive CAD very challenging. These diagnostic tests have been introduced and tested in a population with a much higher probability of disease and therefore the contemporary accuracy of these old tests appear much lower than in the past. In addition, in the past few years the relevance of the traditional ischemia guided coronary intervention strategy has been questioned. Given the low CV events granted by an optimal medical therapy in CAD the major attention has been directed on detecting coronary atherosclerosis. The earlier the better. At the same time, a growing number of data from clinical studies have shown a significant prognostic role for non-obstructive CAD and coronary atherosclerosis. All these facts have shifted the clinicians' attention from the functional evaluation of the coronary circulation to the anatomic burden of disease.

Toward a more reliable characterization of fractal properties of the cerebral cortex of healthy subjects during the lifespan.

The cerebral cortex manifests an inherent structural complexity of folding. The fractal geometry describes the complexity of structures which show self-similarity in a proper interval of spatial scales. In this study, we aimed at evaluating in-vivo the effect of different criteria for selecting the interval of spatial scales in the estimation of the fractal dimension (FD) of the cerebral cortex in T1-weighted magnetic resonance imaging (MRI). We compared four different strategies, including two a priori selections of the interval of spatial scales, an automated selection of the spatial scales within which the cerebral cortex manifests the highest statistical self-similarity, and an improved approach, based on the search of the interval of spatial scales which presents the highest rounded R2adj coefficient and, in case of equal rounded R2adj coefficient, preferring the widest interval in the log-log plot. We employed two public and international datasets of in-vivo MRI scans for a total of 159 healthy subjects (age range 6-85 years). The improved approach showed strong associations of FD with age and yielded the most accurate machine learning models for individual age prediction in both datasets. Our results indicate that the selection of the interval of spatial scales of the cerebral cortex is thus critical in the estimation of FD.

Central modulation of parasympathetic outflow is impaired in de novo Parkinson's disease patients.

Task- and stimulus-based neuroimaging studies have begun to unveil the central autonomic network which modulates autonomic nervous system activity. In the present study, we aimed to evaluate the central autonomic network without the bias constituted by the use of a task. Additionally, we assessed whether this circuitry presents signs of dysregulation in the early stages of Parkinson's disease (PD), a condition which may be associated with dysautonomia. We combined heart-rate-variability based methods for time-varying assessments of the autonomic nervous system outflow with resting-state fMRI in 14 healthy controls and 14 de novo PD patients, evaluating the correlations between fMRI time-series and the instantaneous high-frequency component of the heart-rate-variability power spectrum, a marker of parasympathetic outflow. In control subjects, the high-frequency component of the heart-rate-variability power spectrum was significantly anti-correlated with fMRI time-series in several cortical, subcortical and brainstem regions. This complex central network was not detectable in PD patients. In between-group analysis, we found that in healthy controls the brain activation related to the high-frequency component of the heart-rate-variability power spectrum was significantly less than in PD patients in the mid and anterior cingulum, sensorimotor cortex and supplementary motor area, insula and temporal lobe, prefrontal cortex, hippocampus and in a region encompassing posterior cingulum, precuneus and parieto-occipital cortex. Our results indicate that the complex central network which modulates parasympathetic outflow in the resting state is impaired in the early clinical stages of PD.