The Use of Magnetic Resonance Imaging in Radiation Therapy Treatment Simulation and Planning.

Ever since its introduction as a diagnostic imaging tool the potential of magnetic resonance imaging (MRI) in radiation therapy (RT) treatment simulation and planning has been recognized. Recent technical advances have addressed many of the impediments to use of this technology and as a result have resulted in rapid and growing adoption of MRI in RT. The purpose of this article is to provide a broad review of the multiple uses of MR in the RT treatment simulation and planning process, identify several of the most used clinical scenarios in which MR is integral to the simulation and planning process, highlight existing limitations and provide multiple unmet needs thereby highlighting opportunities for the diagnostic MR imaging community to contribute and collaborate with our oncology colleagues. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 5.

Drug-resistant temporal lobe epilepsy with temporal encephaloceles: How far to resect.

PURPOSE: This study sought to evaluate the impact of surgical extent on seizure outcome in drug-resistant temporal lobe epilepsy (DR-TLE) with temporal encephaloceles (TE). METHODS: This was a single-institution retrospective study of patients who underwent surgery for DR-TLE with TE between January 2008 and December 2020. The impact of surgical extent on seizure outcome was evaluated. In a subset with dominant DR-TLE, the impact of surgical extent on neuropsychometric outcome was evaluated. RESULTS: Thirty-four patients were identified (female, 56%; median age at surgery, 43 years). TE were frequently overlooked on initial magnetic resonance imaging (MRI), with encephaloceles only detected after repeat or expert re-review of MRI, additional multi-modal imaging, or intra-operatively in 31 (91%). Sixteen (47%) underwent limited resections, including encephalocele resection only (n = 5) and encephalocele resection with more extensive temporal corticectomy sparing the amygdala and hippocampus (n = 11). The remainder (n = 18, 53%) underwent standard anterior temporal lobectomy and amygdalohippocampectomy (ATLAH). Limited resection was performed more frequently on the left (12/17 vs. 4/17, p = 0.015). Twenty-seven patients (79%) had a favourable outcome (Engel I/II), and 17 (50%) were seizure-free at the last follow-up (median seizure-free survival of 27.3 months). There was no statistically significant difference in seizure-free outcomes between limited resection and ATLAH. In dominant DR-TLE, verbal memory decline was more likely after ATLAH than limited resection (3/4 vs. 0/9, p = 0.014). CONCLUSION: Expert re-review of imaging and multi-modal advanced imaging improved TE identification. There was no statistical difference in seizure-free outcomes based on surgical extent. Preservation of verbal memory supports limited resection in dominant temporal cases.

EEG Source Localization in Temporal Encephaloceles: Concordance With Surgical Resection and Clinical Outcomes.

PURPOSE: Temporal encephaloceles are a cause of drug-resistant temporal lobe epilepsy; however, their relationship with epileptogenesis is unclear, and optimal surgical resection is uncertain. EEG source localization (ESL) may guide surgical decision-making. METHODS: We reviewed patients at Mayo Clinic Rochester with drug-resistant temporal lobe epilepsy and temporal encephaloceles, who underwent limited resection and had 1-year outcomes. EEG source localization was performed using standard density scalp EEG of ictal and interictal activity. Distance from dipole and standardized low-resolution brain electromagnetic tomography (sLORETA) solutions to the encephalocele were measured. Concordance of ESL with encephalocele and surgical resection was compared with 1-year surgical outcomes. RESULTS: Seventeen patients met criteria. The mean distances from ESL results to encephalocele center for dipole and sLORETA analyses were 23 mm (SD 9) and 22 mm (SD 11), respectively. Ten patients (55.6%) had Engel I outcomes at 1 year. Dipole-encephalocele distance and sLORETA-encephalocele distance were significantly longer in patients with Engel I outcome and patients whose encephalocele was contained by sLORETA had worse outcome as well; however, multiple logistic regression analysis found that only containment of encephalocele by the sLORETA current density was significant (P < 0.05), odds ratio 0.12 (95% confidence interval [0.021, 0.71]). CONCLUSIONS: EEG source localization of scalp EEG localizes near encephaloceles, however, typically not in the encephalocele itself; this may be due to scalp EEG sampling propagated activity or alternatively that the seizure onset zone extends beyond the herniated cortex. Surprisingly, we observed increased ESL to encephalocele distances in patients with excellent surgical outcomes. Larger cohort studies including intracranial EEG data are needed to further explore this finding.

Achieving Control over the Reduction/Coupling Dichotomy of N2 by Boron Metallomimetics.

We report a detailed computational and experimental study of the fixation and reductive coupling of dinitrogen with low-valent boron compounds. Consistent with our mechanistic findings, the selectivity toward nitrogen fixation or coupling can be controlled through either steric bulk or the reaction conditions, allowing for the on-demand synthesis of nitrogen chains. The electronic structure and intriguing magnetic properties of intermediates and products of the reaction of dinitrogen with borylenes are also elucidated using high-level computational approaches.

C-C and C-N Bond Activation, Lewis-Base Coordination and One- and Two-Electron Oxidation at a Linear Aminoborylene.

A cyclic alkyl(amino)carbene (CAAC)-stabilized dicoordinate aminoborylene is synthesized by the twofold reduction of a [(CAAC)BCl2 (TMP)] (TMP=2,6-tetramethylpiperidyl) precursor. NMR-spectroscopic, X-ray crystallographic and computational analyses confirm the cumulenic nature of the central C=B=N moiety. Irradiation of [(CAAC)B(TMP)] (2) resulted in an intramolecular C-C bond activation, leading to a doubly-fused C10 BN heterocycle, while the reaction with acetonitrile resulted in an aryl migration from the CAAC to the acetonitrile nitrogen atom, concomitant with tautomerization of the latter to a boron-bound allylamino ligand. One-electron oxidation of 2 with CuX (X=Cl, Br) afforded the corresponding amino(halo)boryl radicals, which were characterized by EPR spectroscopy and DFT calculations. Placing 2 under an atmosphere of CO afforded the tricoordinate (CAAC,CO)-stabilized aminoborylene. Finally, the twofold oxidation of 2 with chalcogens led, in the case of N2 O and sulfur, to the splitting of the B-CCAAC bond and formation of the 2,4-diamino-1,3,2,4-dichalcogenadiboretanes and CAAC-chalcogen adducts, whereas with selenium a monomeric boraselenone was isolated, which showed some degree of B-Se multiple bonding.

High-content, arrayed compound screens with rhinovirus, influenza A virus and herpes simplex virus infections.

Viruses are genetically and structurally diverse, and outnumber cells by orders of magnitude. They can cause acute and chronic infections, suppress, or exacerbate immunity, or dysregulate survival and growth of cells. To identify chemical agents with pro- or antiviral effects we conducted arrayed high-content image-based multi-cycle infection screens of 1,280 mainly FDA-approved compounds with three human viruses, rhinovirus (RV), influenza A virus (IAV), and herpes simplex virus (HSV) differing in genome organization, composition, presence of an envelope, and tropism. Based on Z'-factors assessing screening quality and Z-scores ranking individual compounds, we identified potent inhibitors and enhancers of infection: the RNA mutagen 5-Azacytidine against RV-A16; the broad-spectrum antimycotic drug Clotrimazole inhibiting IAV-WSN; the chemotherapeutic agent Raltitrexed blocking HSV-1; and Clobetasol enhancing HSV-1. Remarkably, the topical antiseptic compound Aminacrine, which is clinically used against bacterial and fungal agents, inhibited all three viruses. Our data underscore the versatility and potency of image-based, full cycle virus propagation assays in cell-based screenings for antiviral agents.

Evaluation of a New, Highly Flexible Radiofrequency Coil for MR Simulation of Patients Undergoing External Beam Radiation Therapy.

PURPOSE: To evaluate the performance of a new, highly flexible radiofrequency (RF) coil system for imaging patients undergoing MR simulation. METHODS: Volumetric phantom and in vivo images were acquired with a commercially available and prototype RF coil set. Phantom evaluation was performed using a silicone-filled humanoid phantom of the head and shoulders. In vivo assessment was performed in five healthy and six patient subjects. Phantom data included T1-weighted volumetric imaging, while in vivo acquisitions included both T1- and T2-weighted volumetric imaging. Signal to noise ratio (SNR) and uniformity metrics were calculated in the phantom data, while SNR values were calculated in vivo. Statistical significance was tested by means of a non-parametric analysis of variance test. RESULTS: At a threshold of p = 0.05, differences in measured SNR distributions within the entire phantom volume were statistically different in two of the three paired coil set comparisons. Differences in per slice average SNR between the two coil sets were all statistically significant, as well as differences in per slice image uniformity. For patients, SNRs within the entire imaging volume were statistically significantly different in four of the nine comparisons and seven of the nine comparisons performed on the per slice average SNR values. For healthy subjects, SNRs within the entire imaging volume were statistically significantly different in seven of the nine comparisons and eight of the nine comparisons when per slice average SNR was tested. CONCLUSIONS: Phantom and in vivo results demonstrate that image quality obtained from the novel flexible RF coil set was similar or improved over the conventional coil system. The results also demonstrate that image quality is impacted by the specific coil configurations used for imaging and should be matched appropriately to the anatomic site imaged to ensure optimal and reproducible image quality.

Signal intensity of perirolandic cortex identifies the central sulcus on double inversion recovery MRI.

BACKGROUND: Identification of the central sulcus can require inspection of subtle differences or require certain pulse sequences. This study identifies the central sulcus by signal intensity on double inversion recovery (DIR) images in multiple anatomic locations and imaging planes. METHODS: Forty-nine patients (98 hemispheres) were retrospectively reviewed by three neuroradiologists and one radiology resident. The central sulcus was compared to the surrounding sulci for differences in signal intensity at axial hand knob, axial operculum, and lateral convexity sagittal images (294 locations) on DIR images. The use of the "disappearing central sulcus sign" where the window level is increased at constant width and black/white inversion were also assessed. RESULTS: In 49 patients (22 females, 27 males; median age 36 years), the central sulcus cortex signal intensity was lower than adjacent sulci with a frequency of 90/98 (91.8%) at the axial hand knob level, 68/98 (69.4%) at the axial operculum level, and 76/98 (77.5%) at the sagittal level. With black and white inversion, the frequencies were of 96/98 (98%), 92/98 (94%), and 87/98 (89%). The central sulcus was the first to disappear at all three levels with high degrees of inter-reader agreement (86-99%). Traditional anatomic landmarks were absent or conflicting in seven hemispheres (5 patients). The central sulcus was identified by DIR signal intensity in all seven hemispheres. CONCLUSIONS: The central sulcus can be identified by differences in signal intensity of the perirolandic cortex on DIR. Use of black/white inversion and the disappearing central sulcus sign may further facilitate identification.

Microscopy deep learning predicts virus infections and reveals mechanics of lytic-infected cells.

Imaging across scales reveals disease mechanisms in organisms, tissues, and cells. Yet, particular infection phenotypes, such as virus-induced cell lysis, have remained difficult to study. Here, we developed imaging modalities and deep learning procedures to identify herpesvirus and adenovirus (AdV) infected cells without virus-specific stainings. Fluorescence microscopy of vital DNA-dyes and live-cell imaging revealed learnable virus-specific nuclear patterns transferable to related viruses of the same family. Deep learning predicted two major AdV infection outcomes, non-lytic (nonspreading) and lytic (spreading) infections, up to about 20 hr prior to cell lysis. Using these predictive algorithms, lytic and non-lytic nuclei had the same levels of green fluorescent protein (GFP)-tagged virion proteins but lytic nuclei enriched the virion proteins faster, and collapsed more extensively upon laser-rupture than non-lytic nuclei, revealing impaired mechanical properties of lytic nuclei. Our algorithms may be used to infer infection phenotypes of emerging viruses, enhance single cell biology, and facilitate differential diagnosis of non-lytic and lytic infections.

Whole-brain 3D MR fingerprinting brain imaging: clinical validation and feasibility to patients with meningioma.

PURPOSE: MR fingerprinting (MRF) is a MR technique that allows assessment of tissue relaxation times. The purpose of this study is to evaluate the clinical application of this technique in patients with meningioma. MATERIALS AND METHODS: A whole-brain 3D isotropic 1mm3 acquisition under a 3.0T field strength was used to obtain MRF T1 and T2-based relaxometry values in 4:38 s. The accuracy of values was quantified by scanning a quantitative MR relaxometry phantom. In vivo evaluation was performed by applying the sequence to 20 subjects with 25 meningiomas. Regions of interest included the meningioma, caudate head, centrum semiovale, contralateral white matter and thalamus. For both phantom and subjects, mean values of both T1 and T2 estimates were obtained. Statistical significance of differences in mean values between the meningioma and other brain structures was tested using a Friedman's ANOVA test. RESULTS: MR fingerprinting phantom data demonstrated a linear relationship between measured and reference relaxometry estimates for both T1 (r2 = 0.99) and T2 (r2 = 0.97). MRF T1 relaxation times were longer in meningioma (mean ± SD 1429 ± 202 ms) compared to thalamus (mean ± SD 1054 ± 58 ms; p = 0.004), centrum semiovale (mean ± SD 825 ± 42 ms; p < 0.001) and contralateral white matter (mean ± SD 799 ± 40 ms; p < 0.001). MRF T2 relaxation times were longer for meningioma (mean ± SD 69 ± 27 ms) as compared to thalamus (mean ± SD 27 ± 3 ms; p < 0.001), caudate head (mean ± SD 39 ± 5 ms; p < 0.001) and contralateral white matter (mean ± SD 35 ± 4 ms; p < 0.001) CONCLUSIONS: Phantom measurements indicate that the proposed 3D-MRF sequence relaxometry estimations are valid and reproducible. For in vivo, entire brain coverage was obtained in clinically feasible time and allows quantitative assessment of meningioma in clinical practice.

Whole brain 3D MR fingerprinting in multiple sclerosis: a pilot study.

BACKGROUND: MR fingerprinting (MRF) is a novel imaging method proposed for the diagnosis of Multiple Sclerosis (MS). This study aims to determine if MR Fingerprinting (MRF) relaxometry can differentiate frontal normal appearing white matter (F-NAWM) and splenium in patients diagnosed with MS as compared to controls and to characterize the relaxometry of demyelinating plaques relative to the time of diagnosis. METHODS: Three-dimensional (3D) MRF data were acquired on a 3.0T MRI system resulting in isotropic voxels (1 × 1 × 1 mm3) and a total acquisition time of 4 min 38 s. Data were collected on 18 subjects paired with 18 controls. Regions of interest were drawn over MRF-derived T1 relaxometry maps encompassing selected MS lesions, F-NAWM and splenium. T1 and T2 relaxometry features from those segmented areas were used to classify MS lesions from F-NAWM and splenium with T-distributed stochastic neighbor embedding algorithms. Partial least squares discriminant analysis was performed to discriminate NAWM and Splenium in MS compared with controls. RESULTS: Mean out-of-fold machine learning prediction accuracy for discriminant results between MS patients and controls for F-NAWM was 65 % (p = 0.21) and approached 90 % (p < 0.01) for the splenium. There was significant positive correlation between time since diagnosis and MS lesions mean T2 (p = 0.015), minimum T1 (p = 0.03) and negative correlation with splenium uniformity (p = 0.04). Perfect discrimination (AUC = 1) was achieved between selected features from MS lesions and F-NAWM. CONCLUSIONS: 3D-MRF has the ability to differentiate between MS and controls based on relaxometry properties from the F-NAWM and splenium. Whole brain coverage allows the assessment of quantitative properties within lesions that provide chronological assessment of the time from MS diagnosis.

Higher temporal resolution multiband fMRI provides improved presurgical language maps.

PURPOSE: We investigated the hypothesis that increasing fMRI temporal resolution using a multiband (MB) gradient echo-echo planar imaging (GRE-EPI) pulse sequence provides fMRI language maps of higher statistical quality than those acquired with a traditional GRE-EPI sequence. METHODS: This prospective study enrolled 29 consecutive patients receiving language fMRI prior to a potential brain resection for tumor, AVM, or epilepsy. A 4-min rhyming task was performed at 3.0 Tesla with a traditional GRE-EPI pulse sequence (TR = 2000, TE = 30, matrix = 64/100%, slice = 4/0, FOV = 24, slices = 30, time points = 120) and an additional MB GRE-EPI pulse sequence with an acceleration factor of 6 (TR = 333, TE = 30, matrix 64/100%, slice = 4/0, FOV = 24, time points = 720). Spatially filtered t statistical maps were generated. Volumes of interest (VOIs) were drawn around activations at Broca's, dorsolateral prefrontal cortex, Wernicke's, and the visual word form areas. The t value maxima were measured for the overall brain and each of the VOIs. A paired t test was performed for the corresponding traditional and MB GRE-EPI measurements. RESULTS: The mean age of subjects was 42.6 years old (18-75). Sixty-two percent were male. The average overall brain t statistic maxima for the MB pulse sequence (t = 15.4) was higher than for the traditional pulse sequence (t = 9.3, p = < .0001). This also held true for Broca's area (p < 0.0001), Wernicke's area (p < .0001), dorsolateral prefrontal cortex (p < .0001), and the visual word form area (p < .0001). CONCLUSION: A MB GRE-EPI fMRI pulse sequence employing high temporal resolution provides clinical fMRI language maps of greater statistical significance than those obtained with a traditional GRE-EPI sequence.

Reduction and Rearrangement of a Boron(I) Carbonyl Complex.

The one-electron reduction of a cyclic (alkyl)(amino)carbene (CAAC)-stabilized arylborylene carbonyl complex yields a dimeric borylketyl radical anion, resulting from an intramolecular aryl migration to the CO carbon atom. Computational analyses support the existence of a [(CAAC)B(CO)Ar].- radical anion intermediate. Further reduction leads to a highly nucleophilic dianionic (boraneylidene)methanolate.

A high-content image-based drug screen of clinical compounds against cell transmission of adenovirus.

Human adenoviruses (HAdVs) are fatal to immuno-suppressed individuals, but no effective anti-HAdV therapy is available. Here, we present a novel image-based high-throughput screening (HTS) platform, which scores the full viral replication cycle from virus entry to dissemination of progeny and second-round infections. We analysed 1,280 small molecular weight compounds of the Prestwick Chemical Library (PCL) for interference with HAdV-C2 infection in a quadruplicate, blinded format, and performed robust image analyses and hit filtering. We present the entire set of the screening data including all images, image analyses and data processing pipelines. The data are made available at the Image Data Resource (IDR, idr0081). Our screen identified Nelfinavir mesylate as an inhibitor of HAdV-C2 multi-round plaque formation, but not single round infection. Nelfinavir has been FDA-approved for anti-retroviral therapy in humans. Our results underscore the power of image-based full cycle infection assays in identifying viral inhibitors with clinical potential.

The FDA-Approved Drug Nelfinavir Inhibits Lytic Cell-Free but Not Cell-Associated Nonlytic Transmission of Human Adenovirus.

Adenoviruses (AdVs) are prevalent and give rise to chronic and recurrent disease. Human AdV (HAdV) species B and C, such as HAdV-C2, -C5, and -B14, cause respiratory disease and constitute a health threat for immunocompromised individuals. HAdV-Cs are well known for lysing cells owing to the E3 CR1-ß-encoded adenovirus death protein (ADP). We previously reported a high-throughput image-based screening framework and identified an inhibitor of HAdV-C2 multiround infection, nelfinavir mesylate. Nelfinavir is the active ingredient of Viracept, an FDA-approved inhibitor of human immunodeficiency virus (HIV) aspartyl protease that is used to treat AIDS. It is not effective against single-round HAdV infections. Here, we show that nelfinavir inhibits lytic cell-free transmission of HAdV, indicated by the suppression of comet-shaped infection foci in cell culture. Comet-shaped foci occur upon convection-based transmission of cell-free viral particles from an infected cell to neighboring uninfected cells. HAdV lacking ADP was insensitive to nelfinavir but gave rise to comet-shaped foci, indicating that ADP enhances but is not required for cell lysis. This was supported by the notion that HAdV-B14 and -B14p1 lacking ADP were highly sensitive to nelfinavir, although HAdV-A31, -B3, -B7, -B11, -B16, -B21, -D8, -D30, and -D37 were less sensitive. Conspicuously, nelfinavir uncovered slow-growing round HAdV-C2 foci, independent of neutralizing antibodies in the medium, indicative of nonlytic cell-to-cell transmission. Our study demonstrates the repurposing potential of nelfinavir with postexposure efficacy against different HAdVs and describes an alternative nonlytic cell-to-cell transmission mode of HAdV.

Key financial indicators and ratios: How to use them for success in your practice.

Accounting and finance are not typically a core educational offering in medical education. However, for physician leaders and leaders-in-grooming, it is prudent to be familiar with key financial indicators and ratios. The purpose of this review article is to provide fundamental information for emerging radiology physician leaders by describing important financial indicators and ratios, how they are defined and calculated, and, most importantly, how they can be interpreted and utilized for improving practice performance. SUMMARY SENTENCE: Understanding and implementing key financial ratios and indicators is important to maintain and improve financial performance in radiology practices.

Segmentation errors and intertest reliability in automated and manually traced hippocampal volumes.

OBJECTIVE: To rigorously compare automated atlas-based and manual tracing hippocampal segmentation for accuracy, repeatability, and clinical acceptability given a relevant range of imaging abnormalities in clinical epilepsy. METHODS: Forty-nine patients with hippocampal asymmetry were identified from our institutional radiology database, including two patients with significant anatomic deformations. Manual hippocampal tracing was performed by experienced technologists on 3T MPRAGE images, measuring hippocampal volume up to the tectal plate, excluding the hippocampal tail. The same images were processed using NeuroQuant and FreeSurfer software. Ten subjects underwent repeated manual hippocampal tracings by two additional technologists blinded to previous results to evaluate consistency. Ten patients with two clinical MRI studies had volume measurements repeated using NeuroQuant and FreeSurfer. RESULTS: FreeSurfer raw volumes were significantly lower than NeuroQuant (P < 0.001, right and left), and hippocampal asymmetry estimates were lower for both automatic methods than manual tracing (P < 0.0001). Differences remained significant after scaling volumes to age, gender, and scanner matched normative percentiles. Volume reproducibility was fair (0.4-0.59) for manual tracing, and excellent (>0.75) for both automated methods. Asymmetry index reproducibility was excellent (>0.75) for manual tracing and FreeSurfer segmentation and fair (0.4-0.59) for NeuroQuant segmentation. Both automatic segmentation methods failed on the two cases with anatomic deformations. Segmentation errors were visually identified in 25 NeuroQuant and 27 FreeSurfer segmentations, and nine (18%) NeuroQuant and six (12%) FreeSurfer errors were judged clinically significant. INTERPRETATION: Automated hippocampal volumes are more reproducible than hand-traced hippocampal volumes. However, these methods fail in some cases, and significant segmentation errors can occur.

Summary of the First ISMRM-SNMMI Workshop on PET/MRI: Applications and Limitations.

Since the introduction of simultaneous PET/MRI in 2011, there have been significant advancements. In this review, we highlight several technical advancements that have been made primarily in attenuation and motion correction and discuss the status of multiple clinical applications using PET/MRI. This review is based on the experience at the first PET/MRI conference cosponsored by the International Society for Magnetic Resonance in Medicine and the Society of Nuclear Medicine and Molecular Imaging.