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Hyperpolarized 13 C Magnetic Resonance Imaging ( 13 C-MRI) provides a highly sensitive tool to probe tissue metabolism in vivo and has recently been translated into clinical studies. We report the cerebral metabolism of intravenously injected hyperpolarized [1– 13 C]pyruvate in the brain of healthy human volunteers for the first time. Dynamic acquisition of 13 C images demonstrated 13 C-labeling of both lactate and bicarbonate, catalyzed by cytosolic lactate dehydrogenase and mitochondrial pyruvate dehydrogenase respectively. This demonstrates that both enzymes can be probed in vivo in the presence of an intact blood-brain barrier: the measured apparent exchange rate constant (k PL ) for exchange of the hyperpolarized 13 C label between [1– 13 C]pyruvate and the endogenous lactate pool was 0.012 ± 0.006 s −1 and the apparent rate constant (k PB ) for the irreversible flux of [1– 13 C]pyruvate to [ 13 C]bicarbonate was 0.002 ± 0.002 s −1 . Imaging also revealed that [1– 13 C]pyruvate, [1– 13 C]lactate and [ 13 C]bicarbonate were significantly higher in gray matter compared to white matter. Imaging normal brain metabolism with hyperpolarized [1– 13 C]pyruvate and subsequent quantification, have important implications for interpreting pathological cerebral metabolism in future studies.

Cerebral metabolism is tightly regulated and fundamental for healthy neurological function. There is increasing evidence that alterations in this metabolism may be a precursor and early biomarker of later stage disease processes. Proton magnetic resonance spectroscopy (1H-MRS) is a powerful tool to non-invasively assess tissue metabolites and has many applications for studying the normal and diseased brain. However, the technique has limitations including low spatial and temporal resolution, difficulties in discriminating overlapping peaks, and challenges in assessing metabolic flux rather than steady-state concentrations. Hyperpolarized carbon-13 magnetic resonance imaging is an emerging clinical technique that may overcome some of these spatial and temporal limitations, providing novel insights into neurometabolism in both health and in pathological processes such as glioma, stroke and multiple sclerosis. This review will explore the growing body of pre-clinical data that demonstrates a potential role for the technique in assessing metabolism in the central nervous system. There are now a number of clinical studies being undertaken in this area and this review will present the emerging clinical data as well as the potential future applications of hyperpolarized 13C magnetic resonance imaging in the brain, in both clinical and pre-clinical studies.

Simple Summary We evaluated renal cancer with varying aggressive appearances on histology, using an emerging form of non-invasive metabolic MRI. This imaging technique assesses the uptake and metabolism of a breakdown product of glucose (pyruvate) labelled with hyperpolarized carbon-13. We show that pyruvate metabolism is dependent on the aggressiveness of an individual tumor and we provide a mechanism for this finding from tissue analysis of molecules influencing pyruvate metabolism, suggesting a role for its membrane transporter. Abstract Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p < 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer.

Funder: NIHR Cambridge Biomedical Research Centre, Funder: Addenbrooke’s Charitable Trust, Funder: National Institute for Health Research (NIHR), Funder: Mark Foundation For Cancer Research, Funder: Cambridge Commonwealth, European and International Trust, Funder: Cancer Research UK, Funder: Cambridge Clinical Trials Unit, Funder: Cancer Research UK Cambridge Centre, Funder: Engineering and Physical Sciences Research Council Cancer Imaging Centre in Cambridge and Manchester, Funder: Cambridge Experimental Cancer Medicine Centre, PURPOSE: To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI. METHOD: Participants with mRCC undergoing pre-surgical sunitinib therapy in the prospective NeoSun clinical trial (EudraCtNo: 2005-004502-82) were imaged before starting treatment, and after 12 days of sunitinib therapy using morphological MRI sequences, advanced diffusion-weighted imaging, measurements of R2* (related to hypoxia) and dynamic contrast-enhanced imaging. Following nephrectomy, participants continued treatment and were followed-up with contrast-enhanced CT. Changes in imaging parameters before and after sunitinib were assessed with the non-parametric Wilcoxon signed-rank test and the log-rank test was used to assess effects on survival. RESULTS: 12 participants fulfilled the inclusion criteria. After 12 days, the solid and necrotic tumor volumes decreased by 28% and 17%, respectively (p = 0.04). However, tumor-volume reduction did not correlate with progression-free or overall survival (PFS/OS). Sunitinib therapy resulted in a reduction in median solid tumor diffusivity D from 1298x10-6 to 1200x10-6mm2/s (p = 0.03); a larger decrease was associated with a better RECIST response (p = 0.02) and longer PFS (p = 0.03) on the log-rank test. An increase in R2* from 19 to 28s-1 (p = 0.001) was observed, paralleled by a decrease in Ktrans from 0.415 to 0.305min-1 (p = 0.01) and a decrease in perfusion fraction from 0.34 to 0.19 (p

Objective: To explore translational biological and imaging biomarkers for sunitinib treatment before and after debulking nephrectomy in the NeoSun (European Union Drug Regulating Authorities Clinical Trials Database [EudraCT] number: 2005-004502-82) single-centre, single-arm, single-agent, Phase II trial. Patients and Methods: Treatment-naïve patients with metastatic renal cell carcinoma (mRCC) received 50mg once daily sunitinib for 12days pre-surgically, then post-surgery on 4 week-on, 2 week-off, repeating 6-week cycles until disease progression in a single arm phase II trial. Structural and dynamic contrast-enhanced magnet resonance imaging (DCE-MRI) and research blood sampling were performed at baseline and after 12days. Computed tomography imaging was performed at baseline and post-surgery then every two cycles. The primary endpoint was objective response rate (Response Evaluation Criteria In Solid Tumors [RECIST]) excluding the resected kidney. Secondary endpoints included changes in DCE-MRI of the tumour following pre-surgery sunitinib, overall survival (OS), progression-free survival (PFS), response duration, surgical morbidity/mortality, and toxicity. Translational and imaging endpoints were exploratory. Results: A total of 14 patients received pre-surgery sunitinib, 71% (10/14) took the planned 12 doses. All underwent nephrectomy, and 13 recommenced sunitinib postoperatively. In all, 58.3% (seven of 12) of patients achieved partial or complete response (PR or CR) (95% confidence interval 27.7–84.8%). The median OS was 33.7months and median PFS was 15.7months. Amongst those achieving a PR or CR, the median response duration was 8.7months. No unexpected surgical complications, sunitinib-related toxicities, or surgical delays occurred. Within the translational endpoints, pre-surgical sunitinib significantly increased necrosis, and reduced cluster of differentiation-31 (CD31), Ki67, circulating vascular endothelial growth factor-C (VEGF-C), and transfer constant (KTrans, measured using DCE-MRI; all P&nbsp

Molecular imaging techniques have rapidly progressed over recent decades providing unprecedented in vivo characterization of metabolic pathways and molecular biomarkers. Many of these new techniques have been successfully applied in the field of neuro-oncological imaging to probe tumor biology. Targeting specific signaling or metabolic pathways could help to address several unmet clinical needs that hamper the management of patients with brain tumors. This review aims to provide an overview of the recent advances in brain tumor imaging using molecular targeting with positron emission tomography and magnetic resonance imaging, as well as the role in patient management and possible therapeutic implications.

Funder: CRUK and EPSRC Cancer Imaging Centre in Cambridge and Manchester; doi: http://dx.doi.org/10.13039/501100014679, Funder: Engineering and Physical Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000266, Funder: CRUK Cambridge Centre, Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; doi: http://dx.doi.org/10.13039/501100002927, Funder: National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre (BRC), Funder: Experimental Cancer Medicine Centre (ECMC), Funder: The Lundbeck Foundation, Funder: Evelyn Trust; doi: http://dx.doi.org/10.13039/501100004282, Funder: Mark Foundation for Integrative Cancer Research, Measurements of water diffusion with MRI have been used as a biomarker of tissue microstructure and heterogeneity. In this study, diffusion kurtosis tensor imaging (DKTI) of the brain was undertaken in 10 healthy volunteers at a clinical field strength of 3 T. Diffusion and kurtosis metrics were measured in regions-of-interest on the resulting maps and compared with quantitative analysis of normal post-mortem tissue histology from separate age-matched donors. White matter regions showed low diffusion (0.60 ± 0.04 × 10–3 mm2/s) and high kurtosis (1.17 ± 0.06), consistent with a structured heterogeneous environment comprising parallel neuronal fibres. Grey matter showed intermediate diffusion (0.80 ± 0.02 × 10–3 mm2/s) and kurtosis (0.82 ± 0.05) values. An important finding is that the subcortical regions investigated (thalamus, caudate and putamen) showed similar diffusion and kurtosis properties to white matter. Histological staining of the subcortical nuclei demonstrated that the predominant grey matter was permeated by small white matter bundles, which could account for the similar kurtosis to white matter. Quantitative histological analysis demonstrated higher mean tissue kurtosis and vector standard deviation values for white matter (1.08 and 0.81) compared to the subcortical regions (0.34 and 0.59). Mean diffusion on DKTI was positively correlated with tissue kurtosis (r = 0.82, p < 0.05) and negatively correlated with vector standard deviation (r = -0.69, p < 0.05). This study demonstrates how DKTI can be used to study regional structural variations in the cerebral tissue microenvironment and could be used to probe microstructural changes within diseased tissue in the future.

Radiomics, quantitative feature extraction from radiological images, can improve disease diagnosis and prognostication. However, radiomic features are susceptible to image acquisition and segmentation variability. Ideally, only features robust to these variations would be incorporated into predictive models, for good generalisability. We extracted 93 radiomic features from carotid artery computed tomography angiograms of 41 patients with cerebrovascular events. We tested feature robustness to region-of-interest perturbations, image pre-processing settings and quantisation methods using both single- and multi-slice approaches. We assessed the ability of the most robust features to identify culprit and non-culprit arteries using several machine learning algorithms and report the average area under the curve (AUC) from five-fold cross validation. Multi-slice features were superior to single for producing robust radiomic features (67 vs. 61). The optimal image quantisation method used bin widths of 25 or 30. Incorporating our top 10 non-redundant robust radiomics features into ElasticNet achieved an AUC of 0.73 and accuracy of 69% (compared to carotid calcification alone [AUC: 0.44, accuracy: 46%]). Our results provide key information for introducing carotid CT radiomics into clinical practice. If validated prospectively, our robust carotid radiomic set could improve stroke prediction and target therapies to those at highest risk.

Diffusion MRI is a useful tool to investigate the microstructure of brain tumors. However, the presence of fast diffusing isotropic signals originating from non-restricted edematous fluids, within and surrounding tumors, may obscure estimation of the underlying tissue characteristics, complicating the radiological interpretation and quantitative evaluation of diffusion MRI. A multi-shell regularized free water (FW) elimination model was therefore applied to separate free water from tissue-related diffusion components from the diffusion MRI of 26 treatment-naïve glioma patients. We then investigated the diagnostic value of the derived measures of FW maps as well as FW-corrected tensor-derived maps of fractional anisotropy (FA). Presumed necrotic tumor regions display greater mean and variance of FW content than other parts of the tumor. On average, the area under the receiver operating characteristic (ROC) for the classification of necrotic and enhancing tumor volumes increased by 5% in corrected data compared to non-corrected data. FW elimination shifts the FA distribution in non-enhancing tumor parts toward higher values and significantly increases its entropy (p ≤ 0.003), whereas skewness is decreased (p ≤ 0.004). Kurtosis is significantly decreased (p < 0.001) in high-grade tumors. In conclusion, eliminating FW contributions improved quantitative estimations of FA, which helps to disentangle the cancer heterogeneity.

PURPOSE: To assess the potential role of computed tomography (CT) texture analysis (CTTA) in identifying vulnerable patients with carotid artery atherosclerosis. METHODS: In this case-control pilot study, 12 patients with carotid atherosclerosis and a subsequent history of transient ischemic attack or stroke were age and sex matched with 12 control cases with asymptomatic carotid atherosclerosis (follow-up time 103.58 ± 9.2 months). CTTA was performed using a commercially available research software package (TexRAD) by an operator blinded to clinical data. CTTA comprised a filtration-histogram technique to extract features at different scales corresponding to spatial scale filter (fine = 2 mm, medium = 3 mm, coarse = 4 mm), followed by quantification using histogram-based statistical parameters: mean, kurtosis, skewness, entropy, standard deviation, and mean value of positive pixels. A single axial slice was selected to best represent the largest cross-section of the carotid bifurcation or the greatest degree of stenosis, in presence of an atherosclerotic plaque, on each side. RESULTS: CTTA revealed a statistically significant difference in skewness between symptomatic and asymptomatic patients at the medium (0.22 ± 0.35 vs - 0.18 ± 0.39, p < 0.001) and coarse (0.23 ± 0.22 vs 0.03 ± 0.29, p = 0.003) texture scales. At the fine-texture scale, skewness (0.20 ± 0.59 vs - 0.18 ± 0.58, p = 0.009) and standard deviation (366.11 ± 117.19 vs 300.37 ± 82.51, p = 0.03) were significant before correction. CONCLUSION: Our pilot study highlights the potential of CTTA to identify vulnerable patients in stroke and TIA. CT texture may have the potential to act as a novel risk stratification tool in patients with carotid atherosclerosis.

The Special Issue “Advanced Computational Methods for Oncological Image Analysis”, published for the Journal of Imaging, covered original research papers about state-of-the-art and novel algorithms and methodologies, as well as applications of computational methods for oncological image analysis, ranging from radiogenomics to deep learning [...]

Significance Carbon-13 MRI was used to assess exchange of hyperpolarized 13C label between injected [1-13C]pyruvate and the endogenous tumor lactate pool in breast cancer patients. Higher levels of 13C label exchange were observed in more-aggressive tumors, including all triple-negative cancers. The 13C label exchange correlated significantly with the expression of the transmembrane transporter mediating uptake of pyruvate into tumor cells and hypoxia inducible factor 1 (HIF1α), but no significant correlation with the expression of lactate dehydrogenase, the enzyme that catalyzes the exchange. The study has shown that 13C MRI can be used for metabolic imaging of breast cancer patients in the clinic, creating possibilities for noninvasive cancer monitoring in this patient group., Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2−), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2− invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.

Anatomic connections between the cerebral lateral and third ventricles have been mischaracterized since Monro's original erroneous description of his eponymous foramina (FoMs) as being only one T-shaped passage. Accurate knowledge of the in vivo three-dimensional (3D) configuration of FoM has important clinical neuroendoscopic, neurosurgical, and neuroimaging implications. We retrospectively analyzed volumetric high-resolution brain magnetic resonance imaging of 100 normal individuals to characterize the normal spatial anatomy and morphometry for each FoM. We measured the true anatomical 3D angulations of FoMs relative to standard neuroimaging orthogonal planes, and their minimum width, depth, and distance between the medial borders of bilateral FoMs. The right and left FoMs were separate, distinct, and in a V-shaped configuration. Each FoM was a round, oval, or crescent-shaped canal-like passage with well-defined borders formed by the semicircular concavity of the ipsilateral forniceal column. The plane of FoM was angled on average 56.8° ± 9.1° superiorly from the axial plane, 22.5° ± 10.7° laterally, and 37.0° ± 6.9° anteriorly from the midsagittal plane; all these angles changing significantly with increasing age. The mean narrowest diameter of FoM was 2.8 ± 1.2 mm, and its depth was 2.5 ± 0.2 mm. Thus, the true size and orientation of FoM differs from that depicted on standard neuroimaging. Notably, in young subjects, FoM has a diameter smaller than its depth, a configuration akin to a short, small canal. We propose that the eponym "Monro" no longer be associated with this structure, and the term "foramen" be abandoned. Instead, FoM should be more appropriately renamed as the "interventricular canaliculus," or IVC, for short.

Mood disorders (MD) are important and frequent psychiatric illness. The management of patients affected by these conditions represents an important factor of disability as well as a significant social and economic burden. The "in-vivo" studies can help researchers to understand the first developmental events of the pathology and to identify the molecular and non-molecular targets of therapies. However, they have strong limitations due to the fact that human brain circuitry can not be reproduced in animal models. In addition, these neural pathways are difficult to be selectively studied with the modern imaging (such as Magnetic Resonance and Positron Emitted Tomography/Computed Tomography) and non-imaging (such as electroencephalography, magnetoencephalography, transcranial magnetic stimulation and evoked potentials) methods. In comparison with other methods, the "in-vivo" imaging investigations have higher temporal and spatial resolution compared to the "in-vivo" non-imaging techniques. All these factors make difficult to fully understand the aetiology and pathophysiology of these disorders, and consequently hinder the analysis of the effects of pharmacological and non-pharmacological therapies, which have been demonstrated effective in clinical settings. In this review, we will focus our attention on the current state of the art of imaging in the assessment of treatment efficacy in MD. We will analyse briefly the actual classification of MD; then we will focus on the "in vivo" imaging methods used in research and clinical activity, the current knowledge about the neural models at the base of MD. Finally the last part of the review will focus on the analysis of the main markers of response to treatment.

Purpose: The aim of the study is to report radiological findings and features in advanced decomposed bodies obtained by post-mortem computed tomography (PMCT) with autopsy correlation. Materials and methods: This retrospective descriptive multicentric study included 41 forensic cases examined between May 2013 and November 2016. All the bodies were PMCT-scanned prior to autopsy, and internal putrefactive state was determined using the radiological alteration index (RAI) by a radiologist with expertise in forensic radiology and a forensic pathologist trained in forensic imaging. After PMCT scans, grade of external putrefaction (GEP) was assigned during the external examination and the complete autopsy was performed by forensic pathologists. Results: The PMCT images evaluation revealed that the RAI index was > 61 in all bodies, corresponding to a moderate-massive presence of putrefactive gas. The gas grade was > II in correspondence of the major vessels, heart cavities, liver parenchyma, vertebra L3 and subcutaneous pectoral tissues, and varied from I to III in correspondence of the kidney. Cadaveric external examination revealed the presence of advanced transformative phenomena, with a GEP3 and GEP4 in most of the cases, with body swelling, eyes and tongue protrusion, body fluids expulsion and fat liquefaction. Conclusion: Radiological imaging by PMCT as an adjunct to autopsy in advanced decomposed bodies represents a useful tool in detecting post-mortem gas, even in very small amounts. A correct interpretation process of the PMCT data is essential to avoid images pitfalls, due to natural decomposition that can be mistaken for pathologic processes.

The concentration of sodium ions (Na(+)) is raised in solid tumours and can be measured at the cellular, tissue and patient levels. At the cellular level, the Na(+) gradient across the membrane powers the transport of H(+) ions and essential nutrients for normal activity. The maintenance of the Na(+) gradient requires a large proportion of the cell's ATP. Na(+) is a major contributor to the osmolarity of the tumour microenvironment, which affects cell volume and metabolism as well as immune function. Here, we review evidence indicating that Na(+) handling is altered in tumours, explore our current understanding of the mechanisms that may underlie these alterations and consider the potential consequences for cancer progression. Dysregulated Na(+) balance in tumours may open opportunities for new imaging biomarkers and re-purposing of drugs for treatment.

Sophisticated volume measurements of brain structures on magnetic resonance imaging (MRI) may improve specificity in determining long-term progression of multiple sclerosis (MS), but these techniques are laborious. The optic chiasm (OC) is a white matter (WM) structure clearly visible on a routine MRI and is related to the optic nerves (ONs), which are known to atrophy in MS. We hypothesized that OC morphometric measurements would show OC atrophy in MS compared to normal patients. If so, this could help establish a novel simplified brain MRI measure of WM atrophy in MS patients. We retrospectively evaluated standard brain MRIs of 97 patients with known MS and 98 normal individuals. We electronically measured eight OC morphometrics on axial T2WIs and midsagittal T1WIs: OC width and anteroposterior (AP) diameter, diameters of each ON and optic tract (OT), and angles between the ONs or OTs. Mean OC width, AP diameter, and height in MS patients were 11.83 ± 1.25 mm (95% CI 11.58–12.09), 2.99 ± 0.65 mm (95% CI 2.85–3.12), and 2.09 ± 0.37 mm (95% CI 2–2.19), respectively. In normal individuals, they were 12.1 ± 1.4 mm (95% CI 11.78–12.34), 3.43 ± 0.63 mm (95% CI 3.3–3.58), and 2.15 ± 0.37 mm (95% CI 2.07–2.23), respectively. There were statistically significant differences between MS patients and controls for AP diameter (P = 0.000), but not for width (P = 0.204) or height (P = 0.183). The ONs were significantly smaller in MS (P < 0.0017), but not the OTs. Thus, the OC is significantly atrophied in an unstratified cohort of MS patients. Future studies may establish an MRI OC morphometric index to evaluate demyelinating disease in the brain. Clin. Anat. 32:1072–1081, 2019. © 2019 Wiley Periodicals, Inc.

Purpose This prospective study evaluated the use of vascular, extracellular and restricted diffusion for cytometry in tumours (VERDICT) MRI to investigate the tissue microstructure in glioma. VERDICT-derived parameters were correlated with both histological features and tumour subtype and were also used to explore the peritumoural region. Methods Fourteen consecutive treatment-naïve patients (43.5 years ± 15.1 years, six males, eight females) with suspected glioma underwent diffusion-weighted imaging including VERDICT modelling. Tumour cell radius and intracellular and combined extracellular/vascular volumes were estimated using a framework based on linearisation and convex optimisation. An experienced neuroradiologist outlined the peritumoural oedema, enhancing tumour and necrosis on T2-weighted imaging and contrast-enhanced T1-weighted imaging. The same regions of interest were applied to the co-registered VERDICT maps to calculate the microstructure parameters. Pathology sections were analysed with semi-automated software to measure cellularity and cell size. Results VERDICT parameters were successfully calculated in all patients. The imaging-derived results showed a larger intracellular volume fraction in high-grade glioma compared to low-grade glioma (0.13 ± 0.07 vs. 0.08 ± 0.02, respectively; p = 0.05) and a trend towards a smaller extracellular/vascular volume fraction (0.88 ± 0.07 vs. 0.92 ± 0.04, respectively; p = 0.10). The conventional apparent diffusion coefficient was higher in low-grade gliomas compared to high-grade gliomas, but this difference was not statistically significant (1.22 ± 0.13 × 10−3 mm2/s vs. 0.98 ± 0.38 × 10−3 mm2/s, respectively; p = 0.18). Conclusion This feasibility study demonstrated that VERDICT MRI can be used to explore the tissue microstructure of glioma using an abbreviated protocol. The VERDICT parameters of tissue structure correlated with those derived on histology. The method shows promise as a potential test for diagnostic stratification and treatment response monitoring in the future. Key Points • VERDICT MRI is an advanced diffusion technique which has been correlated with histopathological findings obtained at surgery from patients with glioma in this study. • The intracellular volume fraction measured with VERDICT was larger in high-grade tumours compared to that in low-grade tumours. • The results were complementary to measurements from conventional diffusion-weighted imaging, and the technique could be performed in a clinically feasible timescale. Electronic supplementary material The online version of this article (10.1007/s00330-019-6011-8) contains supplementary material, which is available to authorized users.

Objectives To assess whether there is mid-term reorganization in brain networks connectivity after Carotid Endarterectomy (CEA) using resting state functional connectivity Magnetic Resonance (fc-rsMR), with a special focus on the Default Mode Network (DMN). Materials and methods In this prospective exploratory study, 14 asymptomatic consecutive patients (10 males and 4 females, mean age 73.5) with unilateral, significant ICA stenosis eligible for CEA according to European Society for Vascular Surgery guidelines were prospectively recruited. The week before CEA procedure, each patient underwent both neurocognitive and rs-fcMR evaluations on the same day; the neurocognitive test consisted on a Mini Mental State Examination (MMSE). The same neurocognitive test and rs-fcMR examination were repeated on follow-up between 3–6 months after CEA. MMSE scores were compared using paired T-Student Test. Rs-fcMR Region Of Interest (ROI-to-ROI) and Seed-to-voxel group analysis were conducted using the CONN toolbox v18 and the SPM 12 software. Results Patients showed improvements in MMSE scores from before to after CEA (p-value = 0.0001). ROI-to-ROI analysis revealed several statistically significant connectivity changes following CEA, both in terms of positive and negative correlations; Seed-to-Voxel focusing on DMN revealed increased connectivity between medial prefrontal cortex (mPFC) and three different clusters of voxels. Conclusions CEA procedure is associated with an improvement in neurocognitive performance (according to MMSE testing) and reorganization of functional connectivity, including the DMN. These results represent a starting point in order to design further studies for a better understanding of the reorganization of brain networks following CEA, and to investigate the potential role of CEA as a therapeutic procedure for cognitive impairments in selected patients with critical ICA stenosis.

Fully-quantitative MR imaging methods are useful for longitudinal characterization of disease and assessment of treatment efficacy. However, current quantitative MRI protocols have not been widely adopted in the clinic, mostly due to lengthy scan times. Magnetic Resonance Fingerprinting (MRF) is a new technique that can reconstruct multiple parametric maps from a single fast acquisition in the transient state of the MR signal. Due to the relative novelty of this technique, the repeatability and reproducibility of quantitative measurements obtained using MRF has not been extensively studied. Our study acquired test/retest data from the brains of nine healthy volunteers, each scanned on five MRI systems (two at 3.0 T and three at 1.5 T, all from a single vendor) located at two different centers. The pulse sequence and reconstruction algorithm were the same for all acquisitions. After registration of the MRF-derived M0, T1 and T2 maps to an anatomical atlas, coefficients-of-variation (CVs) were computed to assess test/retest repeatability and inter-site reproducibility in each voxel, while a General Linear Model (GLM) was used to determine the voxel-wise variability between all confounders, which included test/retest, subject, field strength and site. Our analysis demonstrated an excellent repeatability (CVs of 2–3% for T1, 5–8% for T2, 3% for normalized-M0) and a good reproducibility (CVs of 3–8% for T1, 8–14% for T2, 5% for normalized-M0) in grey and white matter.

This research investigated local brain connectivity changes following Carotid Endarterectomy (CEA) by connectometry. Seventeen subjects (15 males and 2 females, mean age 74.1years), all eligible for CEA, were prospectively recruited in this exploratory study. On the same day within the week before the CEA, each patient underwent a cognitive evaluation with a Mini Mental State Examination (MMSE) and a Magnetic Resonance Imaging (MRI) exam that included a DTI sequence for the connectometry analysis. A second MMSE and the same MRI protocol were performed on follow-up, 3–6months after CEA. The MMSE scores were analyzed using T-Student tests. The connectometry analysis was performed using a multiple regression model to consider the effect of CEA, choosing three different T-score threshold (T-threshold) values (1, 2 and 3). Results were considered statistically valid for p value adjusted for False Discovery Rate (p-FDR) < 0.05. Comparison of pre-CEA and post-CEA MMSE scores showed improvement of MMSE scores after CEA. Connectometry analysis revealed no areas of statistically significant increased connectivity related to CEA for T-threshold value = 1 and 2, but showed statistically significant increase of connectivity after CEA in both cerebellar hemispheres and corpus callosum for T-threshold value = 3 (p-FDR = 0.0106667). The network property analysis showed improved small worldness (2.14%), clustering coefficient (1.64%), local (1.94%) and global efficiency (0.56%), and reduced characteristic path length (−0.52%) after CEA. These results suggest that CEA is associated both with cognitive performance improvement and changes in interhemispheric local connectivity in the corpus callosum and cerebellum.

Background The goals of neoadjuvant chemotherapy (NAC) are to reduce tumor volume and to offer a prognostic indicator in assessing treatment response. Contrast-enhanced magnetic resonance imaging (CE-MRI) is an established method for evaluating response to NAC in patients with breast cancer. Purpose To validate the role of unenhanced MRI (ue-MRI) compared to CE-MRI for assessing response to NAC in women with breast cancer. Material and Methods Seventy-one patients with ongoing NAC for breast cancer underwent MRI before, during, and at the end of NAC. Ue-MRI was performed with T2-weighted sequences with iterative decomposition of water and fat and diffusion-weighted sequences. CE-MRI was performed using three-dimensional T1-weighted sequences before and after administration of gadobenate dimeglumine. Two blinded observers rated ue-MRI and CE-MRI for the evaluation of tumor response. Statistical analysis was performed to compare lesion size and ADC values changes during therapy, as well as inter-observer agreement. Results There were no statistically significant differences between ue-MRI and CE-MRI sequences for evaluation of lesion size at baseline and after every cycle of treatment ( P > 0.05). The mean tumor ADC values at baseline and across the cycles of NAC were significantly different for the responder group. Conclusion Ue-MRI can achieve similar results to CE-MRI for the assessment of tumor response to NAC. ADC values can differentiate responders from non-responders.

Glucose metabolism in tumours is reprogrammed away from oxidative metabolism, even in the presence of oxygen. Non-invasive imaging techniques can probe these alterations in cancer metabolism providing tools to detect tumours and their response to therapy. Although Positron Emission Tomography with ((18)F)2-fluoro-2-deoxy-D-glucose ((18)F-FDG PET) is an established clinical tool to probe cancer metabolism, it has poor spatial resolution and soft tissue contrast, utilizes ionizing radiation and only probes glucose uptake and phosphorylation and not further downstream metabolism. Magnetic Resonance Spectroscopy (MRS) has the capability to non-invasively detect and distinguish molecules within tissue but has low sensitivity and can only detect selected nuclei. Dynamic Nuclear Polarization (DNP) is a technique which greatly increases the signal-to-noise ratio (SNR) achieved with MR by significantly increasing nuclear spin polarization and this method has now been translated into human imaging. This review provides a brief overview of this process, also termed Hyperpolarized Carbon-13 Magnetic Resonance Spectroscopic Imaging (HP (13)C-MRSI), its applications in preclinical imaging, an outline of the current human trials that are ongoing, as well as future potential applications in oncology.

Background and purpose Hepatitis C virus (HCV) co-infection’s role on cognitive impairment of human immunodeficiency virus (HIV) positive patients is still debated and functional neuroimaging evaluation on this matter is lacking. To provide further insight about HCV’s neuro-effects on HIV associated neurocognitive disorder (HAND), we performed a pilot resting state (RS) functional connectivity magnetic resonance imaging (fcMRI) study to find eventual functional connectivity alteration that could reflect HCV related cognitive performance degradation. Methods Eighteen patients (8 HIV, 10 HIV + HCV), either impaired or not impaired, were assessed with RS fcMRI. A statistic model including cognitive testing results was elaborated during data processing to evaluate brain networks alteration related to actual cognitive status in patients. Results Statistically significant different patterns of connectivity were found: HCV co-infection modified 17 ROIs’ connectivity with 45 supra-threshold connections (p-FDR min 0.0022, max 0.0497). ROIs most involved were right pallidum, brainstem, vermian lobules 1–2 and right cerebellar lobule 10. Graph theory analysis did not demonstrate significant difference between networks, but HCV related modifications at ROI’s local level were found, with particular involvement of ROIs of frontal lobe, basal ganglia and cerebellum. Increased fronto-striatal dysfunctions have been already reported as consequences of HCV infection and could reflect an additive effect. Cerebellar alterations are associated with HIV and HAND, but not with HCV infection, suggesting a synergic effect of HCV. Conclusion Our study demonstrates RS fcMRI can help to understand the interactions between HIV and HCV co-infection, and our preliminary results suggest synergic effects of HCV in HIV-related brain functional modification.

Purpose We aimed to assess if there is a difference of distribution and volume of white matter hyperintensities (WMH) in the brain according to the Circle of Willis (CoW) configuration in patients with carotid artery pathology. Material and methods One-hundred consecutive patients (79 males, 21 females; mean age 70 years; age range 46–84 years) that underwent brain MRI before carotid endarterectomy (CEA) were included. FLAIR-WMH lesion volume was performed using a semi-automated segmentation technique and the status of the circle of Willis was assessed by two neuroradiologists in consensus. Results We found a prevalence of 55% of variants in the CoW configuration; 22 cases had one variants (40%); 25 cases had two variants (45.45%) and 8 cases showed 3 variants (14.55%). The configuration that was associated with the biggest WMH volume and number of lesions was the A1 + PcoA + PcoA. The PcoA variants were the most prevalent and there was no statistically significant difference in number of lesions and WMH for each vascular territory assessed and the same results were found for AcoA and A1 variants. Conclusion Results of our study suggest that the more common CoW variants are not associated with the presence of an increased WMH or number of lesions whereas uncommon configurations, in particular when 2 or more segment are missing increase the WMH volume and number of lesions. The WHM volume of the MCA territory seems to be more affected by the CoW configuration.

Background The purpose of this study was to assess if there is a correlation between the carotid computed tomography (CT) Hounsfield unit (HU)-based plaque attenuation values measured using dual-energy CT (DECT) scanner and brain leukoaraiosis (LA). Methods Fifty consecutive patients (34 males, 16 females; mean age, 69 years; age range, 46-84 years) who underwent carotid CT and brain magnetic resonance imaging were included in the study. CT examinations were performed with a DECT scanner, and LA lesion volume quantification was performed using a semiautomated segmentation technique. Results We found an inverse statistically significant correlation between the HU-based carotid artery plaque attenuation and the LA lesion volume. Because of the presence of calcified plaques, a second model was calculated at low kiloelectron volt levels from 66 to 100 and 100 kV by taking into consideration the fatty and mixed plaques, and this further led to the associations between HU-based attenuation and LA volume in brain and vascular territories. Conclusions The results of our study suggest that the associations between HU attenuation of the carotid artery plaques (with the exclusion of calcified plaques) and the volume of LA are emphasized at low keV energy levels.

$\textbf{BACKGROUND}$: The characterization of small lesions in cirrhotic patients is extremely difficult due to the overlap of imaging features among different entities in the step-way of the hepatocarcinogenesis. The aim of our study was to evaluate the role of gadoxetic-acid MRI in the differentiation of small (≤2 cm) well-differentiated hepatocellular carcinomas from regenerative and dysplastic nodules. $\textbf{METHODS}$: Seventy-three cirrhotic patients, with 118 focal liver lesions (≤2 cm) were prospectively recruited. MRI examination was performed with a 3T magnet and the study protocol included T1 - and T2-weighted pre-contrast sequences and T1 -weighted gadoxetic-acid enhanced post-contrast sequences obtained during the arterial, venous, late dynamic and hepatobiliary phases. All lesions were pathologically confirmed. Two radiologists blinded to clinical and pathological information evaluated two imaging datasets; another radiologist analysed the signal intensity characteristics of each lesion. Sensitivity, specificity and diagnostic accuracy were considered for statistical analysis. $\textbf{RESULTS}$: Good agreement was reported between the two readers (κ 0.70). Both readers reported a significantly improved sensitivity (57.7 and 66.2 vs 74.6 and 83.1) and diagnostic accuracy (0.717 and 0.778 vs 0.843 and 0.901) with the adjunction of the hepatobiliary phase 57.7 vs 74.6 and 66.2 vs 83.1 (p ≤ 0.04). $\textbf{CONCLUSIONS}$: Gadoxetic-acid MRI is a reliable tool for the characterization of HCC and lesions at high risk to further develop.

Arterial tortuosity syndrome (ATS) is an autosomal recessive connective tissue disorder, mainly characterized by tortuosity and elongation of the large- and medium-sized arteries with predisposition to stenoses and aneurysms. ATS is caused by mutations in the SLC2A10 gene, encoding for the facilitative glucose transporter 10 (GLUT10) and is described typically in pediatric patients. We report on a 51-year-old woman, originally ascertained because of unexplained widespread chronic pain and positive family history of aortic malformation. The main findings included aged appearance, congenital joint hypermobility, joint instability complications, chronic fatigue syndrome, progressive painful joint stiffness, abdominal hernias, pelvic prolapses, multiple cardiac valve prolapses, varicose veins, easy bruising, and gingival recession. Vascular imaging revealed kinking and anomalous origin of the aortic arch branches, marked tortuosity of the aorta, pulmonary and most middle arteries, and a small aneurysm of the splenic artery. SLC2A10 analysis disclosed homozygosity for the novel c.1411+1G>A splice mutation, leading to a 41 amino acids GLUT10 internal deletion. Expression study by immunofluorescence using healthy control cells showed lack of membrane internalization of GLUT10 in patient's skin fibroblasts. This report describes the first splice-site SLC2A10 mutation and increases to 19 the repertoire of known mutations in this gene. Comparison with the few previously published adult patients with ATS contributes to the natural history of this condition, which is probably under diagnosed within the expanding family of inherited connective tissue disorders. © 2012 Wiley Periodicals, Inc.

Purpose: To determine whether wide-volume perfusion computed tomography (CT) performed with a new generation scanner can allow evaluation of the effects of chemotherapy combined with antiangiogenetic treatment on the whole tumor mass in patients with locally advanced lung adenocarcinoma and to determine if changes in CT numbers correlate with the response to therapy as assessed by conventional response evaluation criteria in solid tumors (RECIST) Materials and Methods: Forty-five patients with unresectable lung adenocarcinoma underwent perfusion CT before and 40 and 90 days after chemotherapy and antiangiogenetic treatment. RECIST measurements and calculations of blood flow, blood volume, time to peak, and permeability were performed by two independent blinded radiologists. Pearson correlation coefficient was used to assess the correlation between baseline CT numbers. Baseline and follow-up perfusion parameters of the neoplastic lesions were tested overall for statistically significant differences by using the repeatedmeasures analysis of variance and then were also compared on the basis of the therapy response assessed according to the RECIST criteria. Results: Pearson correlation coefficient showed a significant correlation between baseline values of blood flow and blood volume ( ρ = 0.48; P = 001), time to peak and permeability ( ρ = 0.31; P = 04), time to peak and blood flow ( ρ = - 0.66; P < 001), and time to peak and blood volume ( ρ = - 0.39; P = 007). Blood flow, blood volume, and permeability values were higher in responding patients than in the other patients, with a significant difference at second follow-up for blood flow ( P = 0001), blood volume ( P = 02), and permeability ( P = 0001); time to peak was higher in nonresponding patients ( P = 012). Conclusion: Perfusion CT imaging may allow evaluation of lung cancer angiogenesis demonstrating alterations in vascularity following treatment. © RSNA, 2011.

Purpose: This study was done to assess the diagnostic potential of dual-source computed tomography (DSCT) in the functional evaluation of lung cancer patients undergoing surgical resection. The CT data were compared with pulmonary perfusion scintigraphy and pulmonary function tests (PFTs). Materials and methods: All patients were evaluated with DSCT, scintigraphy and PFTs. The DSCT scan protocol was as follows: two tubes (80 and 140 kV; Care Dose protocol); 70 cc of contrast material (5 cc/s); 5- to 6-s scan time; 0.6 mm collimation. After the automatic calculation of lung perfusion with DSCT and quantification of air volumes and emphysema with dedicated software applications, the perfusional CT studies were compared with scintigraphy using a visual score for perfusion defects; CT air volumes and emphysema were compared with PFTs. Results: The values of accuracy, sensitivity, specificity and positive (PPV) and negative (NPV) predictive values of DSCT compared with perfusion scintigraphy as the reference standard were: 0.88, 0.84, 0.90, 0.93 and 0.88, respectively. The McNemar test did not identify significant differences either between the two imaging techniques (p=0.07) or between CT and PFTs (p=0.09). Conclusions: DSCT is a robust and promising technique that provides important and accurate information on lung function. © 2011 Springer-Verlag Italia.

Purpose: The authors performed a preliminary study with blood-pool contrast-enhanced magnetic resonance angiography (MRA) in evaluating the degree of carotid artery stenosis and plaque morphology, comparing the diagnostic performance of first-pass (FP) and steady-state (SS) acquisitions with 64-slice computed tomography angiography (CTA) and using digital subtraction angiography (DSA) as the reference standard. Materials and methods: Twenty patients with ≥50% carotid artery stenosis at Doppler sonography underwent blood-pool contrast-enhanced MRA, CTA and DSA. Two independent radiologists evaluated MRA and CTA examinations to assess the degree of stenosis and characterise plaque morphology. Accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for FP, SS and CTA. The McNemar and Wilcoxon tests were used to determine significant differences (p0.05). Conclusions: Blood-pool contrast-enhanced MRA with SS sequences allow improved diagnostic evaluation of the degree of carotid stenosis and plaque morphology compared with FP and is substantially equal to CTA and DSA. © 2010 Springer-Verlag Italia Riassunto.

Purpose. The aim of this study was to validate a 64-row multidetector computed tomography (64-MDCT) acquisition protocol with biphasic administration of contrast medium for comprehensive assessment of the coronary and systemic arterial tree in a single examination. Materials and methods. The scanning protocol comprised two acquisitions: an electrocardiograph (ECG)-gated scan at the level of the heart, followed by a total-body, low-dose scan of the systemic arterial circulation. Twenty patients were evaluated using two different strategies for contrast administration. In ten patients, the delay between the two acquisitions was set at 40 s, whereas in the remaining patients, it varied between 45 s and 65 s. For both strategies, the degree of systemic arterial opacification and the attenuation gradient between arterial and venous structures were quantitatively assessed at six extracoronary locations. Two observers evaluated in consensus the presence or absence of atherosclerosis and the degree of stenosis of arterial segments. Results. Three hundred coronary segments were analysed. Arterial-wall changes were depicted in 155 (51%) segments, and in 35 (23%), the degree of stenosis was >50%. Of the 640 extracoronary arterial segments, 250 (39%) presented atherosclerotic wall alterations, in 50 (20%), the degree of stenosis was >50% and five were affected by aneurysmal dilatation. The magnitude of arterial opacification values and attenuation gradients between arterial and venous structures were significantly higher in patients scanned with the 40-s fixed-delay strategy. Conclusions. Whole-body CT angiography with biphasic administration of contrast agent and fixed scan delay has been shown to be a feasible and reproducible technique. Comprehensive data on the global atherosclerotic burden potentially offer important therapeutic options for subclinical, high-risk segments. © 2008 Springer-Verlag.

Introduction: In forensic practice, there is a growing need for accurate methods of age estimation, especially in the cases of young individuals of unknown age. Age can be estimated through somatic features that are universally considered associated with chronological age. Unfortunately, these features do not always coincide with the real chronological age: for these reasons that age determination is often very difficult. Our aim is to evaluate accuracy of skeletal age estimation using Tomei’s MRI method in subjects between 12 and 19years old for forensic purposes. Material and methods: Two investigators analyzed MRI images of the left hand and wrist of 77 male and 74 female caucasian subjects, without chronic diseases or developmental disorders, whose age ranged from 12 to 19years. Skeletal maturation was determined by two operators, who analyzed all MRI images separately, in blinded fashion to the chronological age. Inter-rater agreement was measured with Pearson (R2) coefficient. One of the examiners repeated the evaluation after 6months, and intraobserver variation was analyzed. Bland–Altman plots were used to determine mean differences between skeletal and chronological age. Results: Inter-rater agreement Pearson coefficient showed a good linear correlation, respectively, 0.98 and 0.97 in males and females. Bland–Altman analysis demonstrated that the differences between chronological and skeletal age are not significant. Spearman’s correlation coefficient showed good correlation between skeletal and chronological age both in females (R2 = 0.96) and in males (R2 = 0.94). Conclusions: Our results show that MRI skeletal age is a reproducible method and has good correlation with chronological age.

Over the past two decades, systemic neoadjuvant chemotherapy (NAC) has been used in patients with non-metastatic breast cancers [1]. The concept of NAC for operable breast cancers evolved from experience in locally advanced inoperable breast cancer. The goals of NAC in breast cancer are to treat occult systemic disease, decrease the tumor volume reducing the extent of local surgery, and increase long term survival. There are several reasons that support the advantages of NAC. First of all, systemic therapy given prior to surgery might sterilize areas of micrometastases and prevent further cancer growth after the primary tumor is resected [2]. This would be especially true considering the hypothesis that breast surgery could release tumor cells and stimulate the growth of occult micro-metastases through mechanisms such as angiogenesis [3,4]. Another positive aspect of NAC is the possibility to reduce the size of the primary tumor, which allows higher rates of breast-conserving surgery and/or reduces local recurrence rates. Last, the efficacy of NAC can be used as an in vivo assay of drug sensitivity/resistance. In fact, NAC requires an optimal assessment of response to cytotoxic drugs in vivo, which is not only clinically relevant but also critical in terms of research efforts directed to the assessment of chemo resistance and response. Accurate assessment of the neoadjuvant response is a critical element in monitoring and assessing treatment strategies. Considering the high toxicity of chemotherapeutic drugs, early assessment of therapeutic response of the tumor is essential for patient management, as NAC is associated with significant morbidity and reduced quality of life [5,6]. Nowadays, contrast enhanced MRI is considered the most reliable imaging technique in the early assessment of response to NACand it is commonly used in many centers in monitoring NACresponse in patients affected by breast cancer. Several studies have

Purpose To assess the feasibility of using an ultra-low dose (0.05 mmol/kg of body weight [BW]) of high relaxivity contrast agent for late gadolinium enhancement (LGE) imaging in patients with acute myocardial infarction (AMI).Materials and methods 17 consecutive patients (mean age, 60.1 ± 10.3 years) with ST-segment elevation AMI underwent two randomized cardiac magnetic resonance studies (exam intervals between 24 and 48 h) on a 1.5 T unit during the first week after the event using gadobenate dimeglumine (Gd-BOPTA) at the dose of 0.1 mmol/kg BW (standard dose or SD group) and 0.05 mmol/kg BW (half dose or HD group). Image quality was qualitatively assessed. Quantitative analysis of LGE were performed by measuring signal intensity (SI), signal-to-noise ratio (SNR) in the infarcted myocardium (IM), non-infarcted myocardium (N-IM) and left ventricular cavity (LVC) in images acquired at 1, 3, 5, 10, 15 and 20 min after administration of Gd-BOPTA using both contrast media protocol. Contrast-to-noise ratio (CNR) between IM and N-IM (CNR IM/N-IM) and between IM and LVC (CNR IM/LVC) were also quantified for each time point. Moreover the extent of infarcted myocardium was measured.Results 102 LGE images were evaluated for each dose group. Quality score was significantly higher for SD at 1, 15 and 20 min (0.002 < p < 0.046) and for HD at 5 min (p = 0.013). SNR has been higher in the SD group compared to the HD group even though not statistically significant at any time-point for both IM (SD vs. HD: 87.7 ± 73 vs. 65 ± 66; 0.15 < p < 0.38) and N-IM (SD vs. HD: 22 ± 61 vs. 9.9 ± 6.5; 0.09 < p < 0.43). LVC SNR was significantly higher with SD at 10 min (p = 0.03), 15 min (p = 0.001) and 20 min (p = 0.004). CNR between the IM and N-IM was significantly higher using SD compared to HD (1382.24 ± 1049 vs. 695.4 ± 500; 0.000 < p < 0.028) at 10, 15 and 20 min. No significant differences in CNR IM/LVC were noted for HD acquired 5 min after CM administration compared to SD acquired at 10 (p = 0.34), 15 (p = 0.96) and 20 (p = 0.41) min, and between HD at 10 min compared to SD acquired at 15 min (p = 0.78) and 20 min (p = 0.32). Good correlation between SD and HD (0.56 < r2 < 0.85, p < 0.024) was found at all time-points in the measuring of IA.Conclusion The use of a 0.05 mmol/kg dose of gadobenate dimeglumine is feasible for LGE imaging of acute MI and the best image quality is obtained at 5 min after contrast administration. It could be beneficial in patient with renal failure and a solution to improve the identification of subendocardial infarction reducing examination time, costs and total gadolinium load. However, the standard dose of 0.1 mmol/kg provides overall better image quality, with the best performance obtained at the delay of 10 min or more after Gd-BOPTA administration, and it should be routinely preferred.

Objectives: The objectives of this study were to evaluate the efficacy in painmanagement of magnetic resonance (MR)Yguided focused ultrasound for theprimary treatment of painful bone metastases and to assess its potential for localcontrol of bone metastases.Materials and Methods: This was a prospective, single-arm research studywith approval from the institutional review board. Eighteen consecutive patients(female, 8; male, 10; mean [SD] age, 62.7 [11.5] years) with painful bone me-tastases were enrolled. The patients were examined clinically for pain severityand pain interference in accordance with the Brief Pain Inventory-Quality ofLife criteria before and at each follow-up visit. Computed tomography andMR imaging were performed before and at 1 and 3 months after the mag-netic resonanceYguided focused ultrasound treatment. The nonperfused volume(NPV) was calculated to correlate the extension of the ablated pathological tis-sue in the responder and nonresponder patients.Results: No treatment-related adverse events were recorded during the study.The evaluation of pain palliation revealed a statistically significant differencebetween baseline and follow-up values for pain severity and pain interference(P = 0.001, both evaluations). In the evaluation of local tumor control, we ob-served increased bone density with restoration of cortical borders in 5 of the18 patients (27.7%). In accordance with the MD Anderson criteria, completeand partial responses were obtained in 2 of the 18 patients (11.1%) and 4 of the18 patients (22.2%), respectively. Nonperfused volume values ranged between20% and 93%. Mean NPV values remained substantially stable after the treat-ment (P = 0.08). There was no difference in the NPV values between the re-sponder and nonresponder patients (46.7% [24.2%] [25%Y90%] versus 45%[24.9%] [20%Y93%]; P = 0.7).Conclusions: Magnetic resonanceYguided focused ultrasound can be safelyand effectively used as the primary treatment of pain palliation in patientswith bone metastases and has a potential role in local tumor control.Key Words: MRgFUS, high-intensity focused ultrasound, bone metastases,pain palliation, MR-guided interventional radiology, cancer, oncology(Invest Radiol 2013;48: 00Y00)

Purpose: This study was undertaken to prospectively evaluate the diagnostic performance of colour Doppler ultrasonography (CDUS), first-pass (FP) and steady-state (SS) contrast-enhanced magnetic resonance angiography (MRA) and computed tomography angiography (CTA) of the carotid arteries using digital subtraction angiography (DSA) as the reference standard. Materials and methods: A total of 170 patients with previous cerebrovascular events and suspected carotid artery stenoses underwent CDUS, blood-pool MRA, CTA and DSA. Accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for CDUS, FP MRA, SS MRA and CTA. The McNemar and Wilcoxon tests and receiver operating characteristic (ROC) curve analysis were used to determine significant differences (p

OBJECTIVE: The objectives of the study were to determine whether perfusion computed tomography (CT-p) and magnetic resonance diffusion-weighted imaging (MR-DWI) can allow evaluation of the effects of chemotherapy combined with antiangiogenetic treatment on liver metastases in patients with advanced colorectal cancer and to determine if changes in CT-p and MR-DWI correlate with the response to therapy as assessed by conventional Response Evaluation Criteria in Solid Tumors (RECIST). METHODS: Eighteen patients with liver metastases from colorectal cancer underwent CT-p and MR-DWI before and 6 months after chemotherapy and antiangiogenetic treatment. Lesions were classified according to RECIST criteria (complete response [CR], partial response [PR], stable disease [SD], and progressive disease) and calculations of CT-p parameters including blood flow (BF), blood volume (BV), capillary permeability (CP), and MR-DWI apparent diffusion coefficient (ADC) values were performed; RECIST, CT-p, and MR-DWI measurements at baseline and follow-up were tested for statistically significant differences using the paired-samples t test. Baseline and follow-up perfusion parameters of the lesions were also compared on the basis of therapy response assessed by RECIST criteria using independent-samples t test. P < 0.05 was considered indicative of a statistically significant difference for all statistical test. RESULTS: Six patients (6/18; 33.3%) were classified as PR (), and the remaining 12 (12/18; 66.7%) were classified as SD. On a per-lesion basis, 2 (2/32; 6.3%) cannot be identified at follow-up, 6 (6/32; 18.8%) showed a decrease in size of more than 30%, and 24 (24/32; 75%) were substantially stable in size. No cases of progressive disease were demonstrated at follow-up. No statistically significant differences were demonstrated between PR, CR, and SD lesions for BF (P = 0.19), BV (P = 0.14), and ADC (P = 0.68) measurements, whereas CP was significantly higher in CR and PR lesions (P = 0.038). Considering differences between baseline and follow-up values, no statistically significant differences were noted between PR and CR lesions versus SD lesions for CT-p values (BF: P = 0.77; BV: P = 0.15; CP: P = 0.64). A statistically significant difference between PR and CR lesions and SD lesions was noted for ADC values (P = 0.047). CONCLUSION: Both CT-p and MR-DWI can detect therapy-induced modifications in lesion vascularization before significant changes in size are evident. Copyright © 2011 by Lippincott Williams & Wilkins.

Objectives: To optimize the image acquisition parameters for improved steady-state (SS) contrast-enhanced magnetic resonance angiography (CE-MRA) of the carotid arteries with gadobenate dimeglumine. Materials And Methods: An inversion recovery fast low-angle shot (IR-FLASH) sequence for ultrafast determination of the longitudinal relaxation rate R1 was first optimized on phantoms and tested against a routine variable repetition time (TR) spin echo sequence used as reference standard. Different combinations of flip angle (FA, between 6 and 14 degrees) and inversion time (between 134 and 9000 milliseconds) were evaluated to achieve the best trade off between speed and accuracy. The optimized sequence was thereafter used in vivo in 5 subjects to determine the time evolution of blood R1 at 1.5 T after administration of gadobenate dimeglumine at 0.1 mmol/kg bodyweight. An optimal FA for angiographic measurement was thereafter derived from the Ernst equation based on experimental values of R1 previously determined in vivo. Finally, steady-state CE-MRA examinations were performed in 20 subjects to evaluate the improved contrast achieved after optimization of the FA for maximal blood signal enhancement. Results: An ultrafast IR-FLASH sequence with a flip angle of 8 degrees and a properly defined set of inversion time values was shown to give in vitro R1 determinations that were in good agreement with those obtained using a routine, time consuming, variable-TR spin echo sequence. The use of this ultrafast IR-FLASH sequence in vivo allowed the blood signal behavior in the carotid arteries after gadobenate dimeglumine administration to be monitored. Using this sequence, the R 1 decreased from 8.7 ± 0.96 s -1 at 30 seconds after injection to 3.8 ± 0.24 s -1 at 10 minutes after injection. Based on these data for R 1, the optimal FA for SS CE-MRA was calculated to be 18 degrees for a gradient echo acquisition protocol with TR = 7.5 milliseconds, when gadobenate dimeglumine is used. Significantly higher blood signal to noise ratio was achieved on SS images acquired using a three-dimensional spoiled gradient echo sequence with a FA of 18 degrees than on corresponding images acquired with a FA of 35 degrees as used typically for intravascular blood pool contrast agents (52.5 ± 8.3 vs. 29.5 ± 6.0; P < 0.05, Mann-Whitney U test). Conclusion: Detailed experimental knowledge of the in vivo R 1 behavior of blood after gadobenate dimeglumine injection and appropriate modification of the acquisition parameters enables improved signal intensity enhancement on steady-state CE-MRA of the carotid arteries. © 2011 by Lippincott Williams & Wilkins.

Purpose: To assess the feasibility of combined first-pass (FP) and steady-state (SS) contrast-enhanced magnetic resonance angiography (MRA) of the peripheral arteries with gadobenate dimeglumine (MultiHance) and to evaluate diagnostic performance relative to digital subtraction angiography (DSA). Materials and methods: A total of 35 patients with symptomatic peripheral arterial occlusive disease (PAOD) underwent FP MRA (repetition time [TR]/echo time [TE]/flip angle [FA]/acquisition time [TA] = 3.5/1.2/30°/14s) at 1.5T after intravenous injection of 10 mL of gadobenate dimeglumine. Thereafter, SS imaging of the calf (TR/TE/FA/TA = 7.5/2.3/20°/40-130s) and femoropopliteal (TR/TE/FA/TA = 7.5/2.3/18°/130-240s) regions was performed after a second injection of 5 mL of gadobenate dimeglumine. All patients underwent conventional DSA. Three readers reviewed separate FP and FP+SS MRA datasets for image quality and presence/absence of clinically relevant PAOD. A fourth independent observer evaluated DSA images. The diagnostic performance (sensitivity, specificity, positive and negative predictive values) achieved with each dataset was determined and compared. Inter-reader agreement was assessed using kappa statistics. Results: The image quality of 134 of 140 vascular regions was optimal or adequate on SS MRA. Inter-reader agreement was good to very good for assessments of FP (κ = 0.725) and combined FP+SS images (κ = 0.866). SS images improved diagnostic confidence in 34 (48.6%) femoropoliteal and 46 (65.7%) crural regions and altered final diagnosis in 8 (11.4%) and 10 (14.3%) regions, respectively. Global diagnostic accuracy increased from 92.9% on FP images to 95.9% on FP+SS images, with significant (P = 0.0384) improvement in the crural region. Conclusion: SS MRA of the peripheral arteries is feasible with gadobenate dimeglumine and potentially improves diagnostic performance in patients with symptomatic PAOD. © 2011 by Lippincott Williams & Wilkins.

Objective: Quantify the whole-body atherosclerotic disease in asymptomatic subjects with and without metabolic syndrome (MetS) and to assess the contribution of the syndrome and its components to the atherosclerotic burden. Methods: Sixty-five subjects with and 51 without ATPIII-defined MetS underwent a 64-slice computed tomography angiography (CTA). Plaques causing >0% stenosis in coronary or extra-coronary arteries were classified as positive. Results: The prevalence of plaques in coronary, carotid and peripheral arteries as well as their severity did not differ between groups. Conversely, it was seen an almost 3-fold increased likelihood (OR = 2.70; 95% CI 1.30-5.57; P< 0.001) of atherosclerosis in any district across categories of MetS components (0-1 vs. 2-3 vs. 4-5). Hypertriglyceridemia (P< 0.05) and high blood glucose (P< 0.05) were independent predictors of the atherosclerotic burden. Conclusions: Atherosclerotic burden as revealed by 64-TCA appears to be more strongly associated with the number of MetS-related factors than to the clinical diagnosis of MetS itself. © 2011 Elsevier Ireland Ltd.

Purpose: To evaluate the diagnostic performance and effect on therapeutic management of 64-section computed tomographic (CT) angiography in the assessment of steno-occlusive disease in patients with peripheral arterial disease (PAD), with conventional digital subtraction angiography (DSA) as the reference standard. Materials and Methods: The study protocol was approved by the institutional review board, and written informed consent was obtained from all patients. A total of 212 patients with symptomatic PAD underwent CT angiography and subsequent DSA. For stenosis analysis ( ≥70% stenosis), the arterial bed was divided into 35 segments and evaluated by three readers. Interobserver agreement was determined with generalized k statistics. Accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated. In addition, according to the TransAtlantic Inter-Society Consensus (TASC) Document on Management of Peripheral Arterial Disease guidelines, treatment recommendations based on CT angiographic and DSA fi ndings were compared. McNemar test was used to prove signifi cant differences between CT angiographic and DSA fi ndings. Results: A total of 7420 arterial segments were evaluated, with excellent agreement between readers ( κ ≥ 0.928). On a segmental basis, both sensitivity and specifi city for stenosis of 70% or more were at least 96% (3072 of 3113 segments and 4141 of 4279 segments, respectively), with an accuracy of 98% (7213 of 7392 segments), a PPV of 96% (3072 of 3187 segments), an NPV of 99% (3141 of 3187 segments), a PLR of 36.7, and an NLR of 0.013. There was no significant difference between CT angiographic and DSA findings ( P = .62-.87 ). In accordance with TASC II guidelines, 49 patients were referred for conservative treatment, 87 underwent endovascular procedures, 38 underwent surgery, and 17 received hybrid treatment. Therapy recommendations based on CT angiographic fi ndings alone were identical to those based on DSA fi ndings in all but one patient. Conclusion: The diagnostic performance of 64-section CT angiography is excellent in patients with clinical symptoms of PAD. The results can be used to effectively guide therapeutic decision making in these patients. © RSNA, 2011.

Aim: To assess the accuracy of low-dose contrast-enhanced time-resolved 3 T magnetic resonance angiography (MRA) for the morphological and functional assessment of vascular malformations (VM), and to evaluate its diagnostic potential for the depiction of treatment-induced changes. Materials and methods: Twenty-five patients with known VM underwent MRA to evaluate the location and extent of lesions and their haemodynamic characteristics. Three-dimensional (3D) T1-weighted time-resolved sequences were acquired following the administration of 0.05 mmol/kg of gadobenate dimeglumine. VM were classified according to their morphology and haemodynamic characteristics. All patients thereafter underwent conventional angiography to confirm the diagnosis and to treat the lesions (embolization or sclerotherapy). Follow-up MRA was performed 30 days after treatment to assess morphological and functional changes. A visual analogue scale (VAS) was used to clinically assess the severity of symptoms before and after therapy. Results: Based on haemodynamic characteristics, VM were classified as predominantly arterial [4 (16%)], artero-venous [19 (76%)] or venous [2 (8%)]. Twenty-three (92%) lesions were classified as high-flow VM and two (8%) as low-flow VM. Intralesional thrombosis was present in 17 (68%) lesions before therapy and in 10 lesions (40%) after therapy. The median VAS scores were 5 ± 1 before treatment and 4 ± 2 after treatment. Very good correlation (Spearman's correlation coefficient: rho = 0.87; p = 0.000) was noted between the reduction of lesion size on follow-up MRA and pain relief as assessed by VAS. Conclusion: Low-dose contrast-enhanced time-resolved 3 T MRA can be used to define morphological and functional aspects of VM accurately during treatment planning and follow-up, and can identify post-therapy changes that positively correlate with treatment outcome. © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

PURPOSE:: To prospectively evaluate the potential of gadobenate dimeglumine for high-resolution steady-state (SS) contrast-enhanced magnetic resonance angiography (CE-MRA) of the carotid arteries as an adjunct to conventional first-pass (FP) MRA, with computed tomography angiography (CTA) and digital subtraction angiography (DSA) as reference. MATERIALS AND METHODS:: Institutional ethics committee approval and written informed consent were obtained. Forty consecutive patients underwent conventional FP MRA with 15 mL gadobenate dimeglumine, using a conventional 3D FLASH sequence (14 sec acquisition time). Immediately afterward, SS images were obtained using a high resolution coronal 3D FLASH sequence (240 sec acquisition time). All patients also underwent CTA and conventional DSA within 8 ± 3 days. Three experienced radiologists assessed FP and SS image quality and calculated sensitivity, specificity, accuracy, and predictive values for stenosis grade and length, plaque morphology, and tandem lesions using DSA as reference. Detected stenoses were quantified and compared (Spearman rank correlation coefficient, [R(s)]; McNemar test) with DSA and CTA findings. Inter-read variability was assessed using kappa (κ) statistics. The impact of SS acquisitions on diagnostic confidence and patient management was assessed. RESULTS:: MRA FP and SS image quality was excellent in 63 (78.8%) and 46 (57.5%) vessels, adequate in 11 (13.8%) and 20 (25.0%) vessels, and poor in 6 (7.5%) and 14 (17.5%) vessels, respectively. Area under the curve analysis revealed no significant differences between MRA FP, MRA FP + SS, and CTA for the grading of stenoses (P = 0.838; accuracy values of 97.4%, 97.4%, and 98.7%, respectively). Greater accuracy (P < 0.001) was noted for FP + SS images over FP images alone for the assessment of plaque morphology (96.1% for FP + SS images vs. 83.3% for FP). Increased diagnostic confidence was noted for 49 (61.3%) vessels because of additional SS images whereas an impact on final diagnosis was noted in 8 (10%) cases. Good correlation was noted between SS image quality and impact on final diagnosis (R(s) = 0.7; P < 0.0001). CONCLUSION:: SS imaging of the carotid arteries is feasible with gadobenate dimeglumine. The increased spatial resolution attainable allows improved evaluation of stenoses and plaque irregularity, yielding comparable diagnostic performance to that of CTA and DSA. © 2009 by Lippincott Williams & Wilkins.

Purpose: To evaluate the diagnostic accuracy of gadofosveset-enhanced magnetic resonance (MR) angiography in the assessment of carotid artery stenosis, with digital subtraction angiography (DSA) as the reference standard, and to determine the value of reading first-pass, steady-state, and "combined" (first-pass plus steady-state) MR angiograms. Materials and Methods: This study was approved by the local ethics committee, and all subjects gave written informed consent. MR angiography and DSA were performed in 84 patients (56 men, 28 women; age range, 61-76 years) with carotid artery stenosis at Doppler ultrasonography. Three readers reviewed the first-pass, steady-state, and combined MR data sets, and one independent observer evaluated the DSA images to assess stenosis degree, plaque morphology and ulceration, stenosis length, and tandem lesions. Interobserver agreement regarding MR angiographic findings was analyzed by using intraclass correlation and Cohen κ coefficients. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated by using the McNemar test to determine possible significant differences (P < .05). Results: Interobserver agreement regarding all MR angiogram readings was substantial. For grading stenosis, sensitivity, specificity, PPV, and NPV were, respectively, 90%, 92%, 91%, and 91% for first-pass imaging; 95% each for steady-state imaging; and 96%, 99%, 99%, and 97% for combined imaging. For evaluation of plaque morphology, respective values were 84%, 86%, 88%, and 82% for first-pass imaging; 98%, 97%, 98%, and 97% for steady-state imaging; and 98%, 100%, 100%, and 97% for combined imaging. Differences between the first-pass, steady-state, and combined image readings for assessment of stenosis degree and plaque morphology were significant (P < .001). Conclusion: Gadofosveset-enhanced MR angiography is a promising technique for imaging carotid artery stenosis. Steady-state image reading is superior to first-pass image reading, but the combined reading protocol is more accurate. © RSNA, 2009.

This study was performed to validate a highresolution whole-body magnetic resonance angiography (MRA) protocol with parallel imaging and biphasic administration of a single bolus of contrast agent in the preliminary assessment of systemic atherosclerotic burden in patients referred for endovascular procedures. Forty patients referred for endovascular treatment of atherosclerotic disease of the carotid arteries (n=23), peripheral vessels (n=14) or aorta (n=3) on the basis of previous clinical and diagnostic examinations underwent high-resolution whole-body MRA at 1.5 T with 3D spoiled gradient recalled echo (GRE) sequences, featuring parallel imaging acquisition technique with ×2 acceleration factor. Sixty-eight surface coil elements and a four-station imaging protocol were employed. Biphasic intravenous administration of a paramagnetic contrast agent [gadolinium benzyloxyproprionic- tetraacetic acid (Gd-BOPTA)] was performed with the following protocol: 10 ml at a speed of 1 ml/s followed by further 10 ml at a speed of 0.5 ml/s. For image analysis, the arterial system was divided into 42 segments for evaluation. The presence or absence of atherosclerotic lesions was evaluated by two observers in consensus; segments were classified as having clinically significant disease (≥50% stenosis or an aneurysmal dilatation) or no significant disease (

To determine whether CT-perfusion (CT-p) can be used to evaluate the effects of chemotherapy and anti-angiogenic treatment in patients with non-small-cell lung carcinoma (NSCLC) and whether CT-p and standard therapeutic response assessment (RECIST) data obtained before and after therapy correlate.55 patients with unresectable NSCLC underwent CT-p before the beginning of therapy and 50 of them repeated CT-p 90 days after it. Therapeutic protocol included platinum-based doublets plus bevacizumab for non-squamous carcinoma and platinum-based doublets for squamous carcinoma. RECIST measurements and calculations of blood flow (BF), blood volume (BV), time to peak (TTP) and permeability surface (PS) were performed, and baseline and post-treatment measurements were tested for statistically significant differences. Baseline and follow-up perfusion parameters were also compared based on histopathological subclassification (2004 World Health Organization Classification of Tumours) and therapy response assessed by RECIST.Tumour histology was consistent with large cell carcinoma in 14/50 (28%) cases, adenocarcinoma in 22/50 (44%) cases and squamous cell carcinoma in the remaining 14/50 (28%) cases. BF and PS differences for all tumours between baseline and post-therapy measurements were significant (p=0.001); no significant changes were found for BV (p=0.3) and TTP (p=0.1). The highest increase of BV was demonstrated in adenocarcinoma (5.2±34.1%), whereas the highest increase of TTP was shown in large cell carcinoma (6.9±22.4%), and the highest decrease of PS was shown in squamous cell carcinoma (-21.5±18.5%). A significant difference between the three histological subtypes was demonstrated only for BV (p0.007). On the basis of RECIST criteria, 8 (16%) patients were classified as partial response (PR), 2 (4%) as progressive disease (PD) and the remaining 40 (80%) as stable disease (SD). Among PR, a decrease of both BF (18±9.6%) and BV (12.6±9.2%) were observed; TTP increased in 3 (37.5%) cases, and PS decreased in 6 (75%) cases. SD patients showed an increase of BF, BV, TTP and PS in 6 (15%), 21 (52.5%), 23 (57.5%) and 2 (5%) cases, respectively. PD patients demonstrated an increase of BF (26±0.2%), BV (2.7±0.1%) and TTP (3.1±0.8%) while only PS decreased (23±0.2%).CT-p can adequately evaluate therapy-induced alterations in NSCLC, and perfusion parameters correlate with therapy response assessment performed with RECIST criteria.Evaluating perfusional parameters, CT-p can demonstrate therapy-induced changes in patients with different types of lung cancer and identify response to treatment with excellent agreement to RECIST measurements.