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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.

The tumor microenvironment is characteristically acidic and this extracellular acidosis is known to play a role in carcinogenesis and metastasis and can affect tumor chemosensitivity and radiosensitivity. Intracellular pH has been used as a possible biomarker of salvageable tissue in ischemic stroke. A non-invasive MRI-based approach for the determination and imaging of cerebral pH would be a powerful tool in cancer diagnosis and monitoring, as well as stroke treatment planning. Several pH-based MRI imaging approaches have been proposed but for these to be useful, disentangling the effects of pH from other parameters which may affect the measured MRI signal is crucial to ensure accuracy and specificity. R 1 relaxation in the rotating frame (R 1ρ ) is an example of a method that has been proposed to probe pH in vivo using MRI. In this study, we have investigated the relationship between R 1ρ , pH, and macromolecular density in vitro using phantoms and in human volunteers. Here we show that the rate of R 1ρ relaxation (=1/T 1ρ ) varies with pH but only in the presence of macromolecules. At constant pH, phantom macromolecular density inversely correlated with R 1ρ . R 1ρ imaging of the normal human brain demonstrated regional heterogeneity with significant differences between structurally distinct regions, which are likely to be independent of pH. For example, R 1ρ was higher in the basal ganglia compared to grey matter and higher in grey matter compared to white matter. We conclude that R 1ρ cannot be reliably used to image tissue pH without deconvolution from the effects of local tissue macromolecular composition.

Sodium MRI ( 23 Na-MRI) has been used to non-invasively quantify tissue sodium but has been limited by low spatial resolution. Here we demonstrate for the first time that high resolution 23 Na-MRI reveals the spatial heterogeneity of sodium concentration within a multiple sclerosis (MS) lesion. A patient with treatment-naïve relapsing-remitting MS and a ring-enhancing lesion was imaged using 23 Na-MRI. The periphery of the lesion demonstrated an elevated total sodium content compared to the normal appearing white and grey matter (p < 0.01), as well as a heterogeneous distribution of both the total tissue sodium concentration and the intracellular-weighted sodium concentration.

Hyperpolarized 13C MR Spectroscopic Imaging (MRSI) can be used to probe human metabolism in vivo in real time. To date, this has been applied to studies of [1-13C] pyruvate metabolism in oncology and in the healthy human heart (1-3). Here we describe initial results from the first study to image [1-13C] pyruvate metabolism in the healthy human brain. The results show the feasibility of imaging the exchange of hyperpolarized 13C label between pyruvate and the endogenous lactate pool in the healthy brain as well as spectroscopic measurements of 13C-bicarbonate production.

Methods: Fifty consecutive consenting patients who underwent routine 18F-FDG PET/CT for potentially radically treatable lung cancer following a staging CT scan were recruited for PET/MR imaging on the same day. Two experienced readers, unaware of the results with the other modalities, interpreted the PET/MR images independently. Discordances were resolved in consensus. PET/MR TNM staging was compared to surgical staging from thoracotomy as the reference standard in 33 patients. In the remaining 17 nonsurgical patients, TNM was determined based on histology from biopsy, imaging results (CT and PET/CT) and follow-up. ROC curve analysis was used to assess accuracy, sensitivity and specificity of the PET/MR in assessing the surgical resectability of primary tumour. The kappa statistic was used to assess interobserver agreement in the PET/MR TNM staging. Two different readers, without knowledge of the PET/MR findings, subsequently separately reviewed the PET/CT images for TNM staging. The generalized kappa statistic was used to determine intermodality agreement between PET/CT and PET/MR for TNM staging.Results: ROC curve analysis showed that PET/MR had a specificity of 92.3% and a sensitivity of 97.3% in the determination of resectability with an AUC of 0.95. Interobserver agreement in PET/MR reading ranged from substantial to perfect between the two readers (Cohen’s kappa 0.646–1) for T stage, N stage and M stage. Intermodality agreement between PET/CT and PET/MR ranged from substantial to almost perfect for T stage, N stage and M stage (Cohen’s kappa 0.627–0.823).Conclusion: In lung cancer patients PET/MR appears to be a robust technique for preoperative staging.Purpose: To assess the diagnostic performance of PET/MR in patients with non-small-cell lung cancer.

Pancreatic cancer is the fourth cause of mortality worldwide while liver cancer is the sixth most common cancer worldwide. Despite the constant development of non-invasive ablative technique, these two tumours represent still a challenge for oncology due to relatively low survival and poor prognosis. Ultrasound-guided high intensity focused ultrasound (USgFUS) ablation has been proved as a feasible treatment option in patients with pancreatic cancer and hepatocellular carcinoma (HCC). Given relative intrinsic limit of the US guidance, we believe that MR-guided focused ultrasound surgery (MRgFUS) represents the natural evolution of USgFUS. MRgFUS combines the high intensity focused ultrasound (HIFU) induced ablation to the MR capability to depict the anatomical structure as well as to monitor real-time changes in temperature. Notwithstanding the recent widespread of MRgFUS to treat several solid tumours, there is still limited evidence on safety and efficacy of this technique to treat patients with advanced pancreatic carcinoma and HCC. In this paper we present the results of our experience and discuss advantages and limitations of this promising technique. Our results demonstrate the feasibility and safety of MRgFUS in pain relief as well as in decreasing tumor growth and tumor size in both pathologies. Moreover we observed no significant adverse or complications during and after the procedure.

In the article that appeared on page 690 of the November/December 2011 issue, an author’s last name was incorrectly attributed as Marincola. The author’s last name is correctly Cavallo Marincola.

Lesions arising in or around the pineal gland comprise a heterogeneous group of pathologies ranging from benign non-neoplastic cysts to highly malignant neoplasms. Pineal cysts are frequently encountered as an incidental finding in daily radiology practice but there is no universal agreement on the criteria for, frequency of, and duration of follow-up imaging. Solid pineal neoplasms pose a diagnostic challenge owing to considerable overlap in their imaging characteristics, although a combination of radiological appearances, clinical findings, and tumour markers allows for narrowing of the differential diagnosis. In this review, we describe the radiological anatomy of the pineal region, clinical symptoms, imaging appearances, and differential diagnosis of lesions arising in this area, and highlight the clinical management of these conditions.

OBJECTIVEOssification of pterygoalar and pterygospinous ligaments traversing the superior aspect of the infratemporal fossa results in formation of osseous bars that can obstruct percutaneous needle access to the trigeminal ganglion through the foramen ovale (FO), interfere with lateral mandibular nerve block, and impede transzygomatic surgical approaches. Presence of these ligaments has been studied on dry skulls, but description of their radiological anatomy is scarce, in particular on cross-sectional imaging. The aim of this study was to describe visualization of pterygoalar and pterygospinous bars on computed tomography (CT) and to review their prevalence and clinical significance.METHODSThe authors retrospectively reviewed 200 helical sinonasal CT scans by analyzing 0.75- to 1.0-mm axial images, maximum intensity projection (MIP) reconstructions, and volume rendered (VR) images, including views along the anticipated axis of the needle in percutaneous Hartel and submandibular approaches to the FO.RESULTSOssified pterygoalar and pterygospinous ligaments were readily identifiable on CT scans. An ossified pterygoalar ligament was demonstrated in 10 patients, including 1 individual with bilateral complete ossification (0.5%), 4 patients with unilateral complete ossification (2.0%), and 5 with incomplete unilateral ossification (2.5%). Nearly all patients with pterygoalar bars were male (90%, p < 0.01). An ossified pterygospinous ligament was seen in 35 patients, including 2 individuals with bilateral complete (1.0%), 8 with unilateral complete (4%), 8 with bilateral incomplete (4.0%), 12 with bilateral incomplete (6.0%) ossification, and 5 (2.5%) with mixed ossification (complete on one side and incomplete on the contralateral side). All pterygoalar bars interfered with a hypothetical needle access to the FO using the Hartel approach but not the submandibular approach. In contrast, 54% of complete and 24% of incomplete pterygospinous bars impeded the submandibular approach to the FO, without affecting the Hartel approach.CONCLUSIONSThis study provides the first detailed description of cross-sectional radiological and applied surgical anatomy of pterygoalar and pterygospinous bars. Our data are clinically useful during skull base imaging to predict potential obstacles to percutaneous cannulation of the FO and assist in the choice of approach, as these two variants differentially impede the Hartel and submandibular access routes. Our results can also be useful in planning surgical approaches to the skull base through the infratemporal fossa.

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 [...]

No abstract is available for this article.

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.