May 2017
Implementing Lung Cancer Screening: the US Experience.The reduced lung cancer mortality observed with low-dose computed tomography (LDCT) screening in the National Lung Screening Trial (NLST) has led to annual screening in the United States as a covered benefit by both private insurers and the federal health insurance programme, the Centers for Medicare and Medicaid Services. Reimbursement for screening requires data submission to a federal registry on all individuals, whether privately or federally insured. Data must document individual patient eligibility as well as shared decision-making regarding the benefits and risks of LDCT screening, smoking cessation counselling, and the importance of annual screening. Beyond these requirements lie opportunities to maximise the benefits of screening in the radiology setting. Individuals eligible for screening account for a minority of those diagnosed with lung cancer in the US; the evidence needed to improve patient selection must be collected systematically for both screen-detected and incidentally detected lung nodules. Current nodule management and tracking guidelines reduce the false-positive rates observed in the NLST, but fall short in their ability to correctly classify nodules as benign or malignant. Smoking cessation is inadequately managed in most busy clinician practices. As a common nidus for tobacco-associated lung diseases, imagers are uniquely poised to collect the longitudinal data to better inform screening eligibility and to improve indeterminate nodule management, while maximising the setting of screening to motivate and provide smoking cessation. By re-engineering the notion of imaging practice, radiologists can be major contributors to lung cancer early detection and mortality reduction.
May 2017
Irreversible Electroporation: Defining the MRI Appearance of the Ablation Zone With Histopathologic Correlation in a Porcine Liver Model.OBJECTIVE: The purpose of this study is to evaluate the MRI appearance of the irreversible electroporation zone in porcine liver, with histopathologic correlation. MATERIALS AND METHODS: Nine irreversible electroporation ablations were percutaneously created in two Yorkshire pigs. Irreversible electroporation was performed with a bipolar 16-gauge electrode with 3-cm exposure tip and fixed 8-mm interpolar distance. Gadoxetate disodium-enhanced 3-T MRI was performed 50 hours after irreversible electroporation. Livers were harvested immediately after MRI for histopathologic analysis. Ablation zone size was measured on each pulse sequence and correlated with pathologic ablation zone size. Qualitative MRI features of the ablation zone were assessed, and contrast-to-noise ratios (CNRs) were calculated. Statistical analysis included Pearson correlation and t tests.
May 2017
De Novo Loss-of-function Variants in STAG2 are Associated with Developmental Delay, Microcephaly, and Congenital Anomalies.The cohesin complex is an evolutionarily conserved multi-subunit protein complex which regulates sister chromatid cohesion during mitosis and meiosis. Additionally, the cohesin complex regulates DNA replication, DNA repair, and transcription. The core of the complex consists of four subunits: SMC1A, SMC3, RAD21, and STAG1/2. Loss-of-function mutations in many of these proteins have been implicated in human developmental disorders collectively termed "cohesinopathies." Through clinical exome sequencing (CES) of an 8-year-old girl with a clinical history of global developmental delay, microcephaly, microtia with hearing loss, language delay, ADHD, and dysmorphic features, we describe a heterozygous de novo variant (c.205C>T; p.(Arg69*)) in the integral cohesin structural protein, STAG2. This variant is associated with decreased STAG2 protein expression. The analyses of metaphase spreads did not exhibit premature sister chromatid separation; however, delayed sister chromatid cohesion was observed. To further support the pathogenicity of STAG2 variants, we identified two additional female cases from the DECIPHER research database with mutations in STAG2 and phenotypes similar to our patient. Interestingly, the clinical features of these three cases are remarkably similar to those observed in other well-established cohesinopathies. Herein, we suggest that STAG2 is a dosage-sensitive gene and that heterozygous loss-of-function variants lead to a cohesinopathy.
May 2017
Safety and Immunogenicity of Adenovirus 35 Tuberculosis Vaccine Candidate in Adults with Active or Previous Tuberculosis. A Randomized Trial.RATIONALE: Administration of tuberculosis (TB) vaccines in participants with previous or current pulmonary TB may have the potential for causing harmful postvaccination immunologic (Koch-type) reactions. OBJECTIVES: To assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored TB candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary TB. METHODS: We performed a phase II randomized, placebo-controlled, double-blinded dose-escalation study in an HIV-negative adult South African cohort (n = 72) with active pulmonary TB (on treatment for 1-4 mo) or pulmonary TB treated at least 12 months before study entry and considered cured. Safety endpoints included clinical assessment, flow volume curves, diffusing capacity of the lung for carbon monoxide, pulse oximetry, chest radiograph, and high-resolution thoracic computerized tomography scans. Cytokine expression by CD4 and CD8 T cells, after stimulation with Ag85A, Ag85B, and TB10.4 peptide pools, was examined by intracellular cytokine staining.
April 2017
Obstructive Pulmonary Disease in Patients with Previous Tuberculosis: Pathophysiology of a Community-based Cohort.BACKGROUND: An association between chronic airflow limitation (CAL) and a history of pulmonary tuberculosis (PTB) has been confirmed in epidemiological studies, but the mechanisms responsible for this association are unclear. It is debated whether CAL in this context should be viewed as chronic obstructive pulmonary disease (COPD) or a separate phenotype. OBJECTIVE: To compare lung physiology and high-resolution computed tomography (HRCT) findings in subjects with CAL and evidence of previous (healed) PTB with those in subjects with smoking-related COPD without evidence of previous PTB. METHODS: Subjects with CAL identified during a Burden of Obstructive Lung Disease (BOLD) study performed in South Africa were studied. Investigations included questionnaires, lung physiology (spirometry, body plethysmography and diffusing capacity) and quantitative HRCT scans to assess bronchial anatomy and the presence of emphysema (<-950 HU), gas trapping (<-860 HU) and fibrosis (>-200 HU). Findings in subjects with a past history and/or HRCT evidence of PTB were compared with those in subjects without these features.
April 2017
Modified Criteria for Radiographic Response Assessment in Glioblastoma Clinical Trials.Radiographic endpoints including response and progression are important for the evaluation of new glioblastoma therapies. The current RANO criteria was developed to overcome many of the challenges identified with previous guidelines for response assessment, however, significant challenges and limitations remain. The current recommendations build on the strengths of the current RANO criteria, while addressing many of these limitations. Modifications to the current RANO criteria include suggestions for volumetric response evaluation, use contrast enhanced T1 subtraction maps to increase lesion conspicuity, removal of qualitative non-enhancing tumor assessment requirements, use of the post-radiation time point as the baseline for newly diagnosed glioblastoma response assessment, and "treatment-agnostic" response assessment rubrics for identifying pseudoprogression, pseudoresponse, and a confirmed durable response in newly diagnosed and recurrent glioblastoma trials.
April 2017
Respiratory Motion-resolved, Self-gated 4D-MRI Using Rotating Cartesian K-space (ROCK).PURPOSE: To propose and validate a respiratory motion resolved, self-gated (SG) 4D-MRI technique to assess patient-specific breathing motion of abdominal organs for radiation treatment planning. METHODS: The proposed 4D-MRI technique was based on the balanced steady-state free-precession (bSSFP) technique and 3D k-space encoding. A novel rotating cartesian k-space (ROCK) reordering method was designed which incorporates repeatedly sampled k-space centerline as the SG motion surrogate and allows for retrospective k-space data binning into different respiratory positions based on the amplitude of the surrogate. The multiple respiratory-resolved 3D k-space data were subsequently reconstructed using a joint parallel imaging and compressed sensing method with spatial and temporal regularization. The proposed 4D-MRI technique was validated using a custom-made dynamic motion phantom and was tested in six healthy volunteers, in whom quantitative diaphragm and kidney motion measurements based on 4D-MRI images were compared with those based on 2D-CINE images.
April 2017
Risk of Vigabatrin-associated Brain Abnormalities on MRI in the Treatment of Infantile Spasms is Dose-dependent.OBJECTIVE: Although the link between vigabatrin (VGB) and retinotoxicity is well known, little attention has been focused on the risk of VGB-associated brain abnormalities on magnetic resonance imaging (MRI) (VABAM), namely reversible-and largely asymptomatic-signal changes in the thalami, basal ganglia, brainstem tegmentum, and cerebellar nuclei. Using a large infantile spasms cohort, we set out to identify predictors of these phenomena. METHODS: Children with infantile spasms were retrospectively identified. Brain MRI reports were serially reviewed without knowledge of VGB exposure. Upon VABAM discovery, records were systematically reviewed to ascertain presence of symptoms attributable to VGB. Separately, progress notes were sequentially reviewed to identify and quantify VGB exposure.
April 2017
Anatomic Variations in Pituitary Endocrinopathies: Implications for the Surgical Corridor.Objectives/Hypotheses Functioning pituitary adenomas may produce endocrinopathies such as acromegaly and Cushing syndrome. Both conditions lead to characteristic anatomic variations as a result of hormonally induced abnormal soft tissue deposition. We evaluate the anatomic differences between acromegalics and Cushing disease patients and compare these dimensions to controls. Design Radiographic review of preoperative magnetic resonance images (MRI) of the pituitary gland. Setting Tertiary academic medical center. Participants Patients who underwent transnasal, transsphenoidal surgery for pituitary adenomas found to have acromegaly or pituitary Cushing between January 1, 2007 and September 1, 2015. A total of 15 patients with similar MRIs and no history of pituitary or sinonasal disease were selected as controls. Main Outcome Measures Dimensions assessed were intercarotid distance; carotid canal width; piriform aperture width; distance from the piriform aperture to the anterior face of the sphenoid; sphenoid sinus height, width, and length; angle from anterior nasal spine to anteroinferior face of sphenoid sinus; choanal height; and nasal cavity height at the level of the vertical segment of the middle turbinate. Sphenoid sinus pneumatization patterns were recorded.
April 2017
Myocardial T1 Mapping for Patients with Implanted Cardiac Devices Using Wideband Inversion Recovery Spoiled Gradient Echo Readout.PURPOSE: To develop and validate a technique for myocardial T1 mapping in patients with implantable cardioverter defibrillators (ICDs). METHODS: A MOLLI-based pulse sequence, named Wideband-FLASH-MOLLI, was developed by incorporating a fast low angle shot (FLASH) readout and a wideband inversion pulse. The performance of Wideband-FLASH-MOLLI was evaluated using phantom studies and validated in eight healthy volunteers and ten patients with ICDs at 1.5 Tesla. Comparisons were made between Wideband-FLASH-MOLLI, FLASH-MOLLI, and bSSFP-MOLLI sequences.
April 2017
In-Bore 3-T MR-guided Transrectal Targeted Prostate Biopsy: Prostate Imaging Reporting and Data System Version 2-based Diagnostic Performance for Detection of Prostate Cancer.PURPOSE: To determine the diagnostic yield of in-bore 3-T magnetic resonance (MR) imaging-guided prostate biopsy and stratify performance according to Prostate Imaging Reporting and Data System (PI-RADS) versions 1 and 2. MATERIALS AND METHODS: This study was HIPAA compliant and institution review board approved. In-bore 3-T MR-guided prostate biopsy was performed in 134 targets in 106 men who (a) had not previously undergone prostate biopsy, (b) had prior negative biopsy findings with increased prostate-specific antigen (PSA) level, or (c) had a prior history of prostate cancer with increasing PSA level. Clinical, diagnostic 3-T MR imaging was performed with in-bore guided prostate biopsy, and pathology data were collected. The diagnostic yields of MR-guided biopsy per patient and target were analyzed, and differences between biopsy targets with negative and positive findings were determined. Results of logistic regression and areas under the curve were compared between PI-RADS versions 1 and 2.
April 2017
Improved Cough and Cough-Specific Quality of Life in Patients Treated for Scleroderma-Related Interstitial Lung Disease: Results of Scleroderma Lung Study II.BACKGROUND: Cough is a common symptom of scleroderma-related interstitial lung disease (SSc-ILD), but its relationship to other characteristics of SSc-ILD, impact on cough-specific quality of life (QoL), and response to therapy for SSc-ILD have not been well studied. METHODS: We investigated frequent cough (FC) in patients with SSc-ILD (N = 142) enrolled in the Scleroderma Lung Study II, a randomized controlled trial comparing mycophenolate mofetil (MMF) and oral cyclophosphamide (CYC) as treatments for interstitial lung disease (ILD). We determined the impact of FC on QoL (Leicester Cough Questionnaire [LCQ]), evaluated the change in FC in response to treatment for SSc-ILD, and examined the relationship between gastroesophageal reflux disease (GERD) and cough during the trial.
April 2017
Aortic Volumetry at Contrast-Enhanced Magnetic Resonance Angiography: Feasibility as a Sensitive Method for Monitoring Bicuspid Aortic Valve Aortopathy.OBJECTIVES: Bicuspid aortic valve patients can develop thoracic aortic aneurysms and therefore require serial imaging to monitor aortic growth. This study investigates the reliability of contrast-enhanced magnetic resonance angiography (CEMRA) volumetry compared with 2-dimensional diameter measurements to identify thoracic aortic aneurysm growth. MATERIALS AND METHODS: A retrospective, institutional review board-approved, and Health Insurance Portability and Accountability Act-compliant study was conducted on 20 bicuspid aortic valve patients (45 ± 8.9 years, 20% women) who underwent serial CEMRA with a minimum imaging follow-up of 11 months. Magnetic resonance imaging was performed at 1.5 T with electrocardiogram-gated, time-resolved CEMRA. Independent observers measured the diameter at the sinuses of Valsalva (SOVs) and mid ascending aorta (MAA) as well as ascending aorta volume between the aortic valve annulus and innominate branch. Intraobserver/interobserver coefficient of variation (COV) and intraclass correlation coefficient (ICC) were computed to assess reliability. Growth rates were calculated and assessed by Student t test (P < 0.05, significant). The diameter of maximal growth (DMG), defined as the diameter at SOV or MAA with the faster growth rate, was recorded.
April 2017
Non-uniformly Weighted Sampling for Faster Localized Two-dimensional Correlated Spectroscopy of the Brain in vivo.Two-dimensional localized correlated spectroscopy (2D L-COSY) offers greater spectral dispersion than conventional one-dimensional (1D) MRS techniques, yet long acquisition times and limited post-processing support have slowed its clinical adoption. Improving acquisition efficiency and developing versatile post-processing techniques can bolster the clinical viability of 2D MRS. The purpose of this study was to implement a non-uniformly weighted sampling (NUWS) scheme for faster acquisition of 2D-MRS. A NUWS 2D L-COSY sequence was developed for 7T whole-body MRI. A phantom containing metabolites commonly observed in the brain at physiological concentrations was scanned ten times with both the NUWS scheme of 12:48 duration and a 17:04 constant eight-average sequence using a 32-channel head coil. 2D L-COSY spectra were also acquired from the occipital lobe of four healthy volunteers using both the proposed NUWS and the conventional uniformly-averaged L-COSY sequence. The NUWS 2D L-COSY sequence facilitated 25% shorter acquisition time while maintaining comparable SNR in humans (+0.3%) and phantom studies (+6.0%) compared to uniform averaging. NUWS schemes successfully demonstrated improved efficiency of L-COSY, by facilitating a reduction in scan time without affecting signal quality.
April 2017
Performance of Relative Enhancement on Multiphasic MRI for the Differentiation of Clear Cell Renal Cell Carcinoma (RCC) From Papillary and Chromophobe RCC Subtypes and Oncocytoma.OBJECTIVE: The objective of our study was to investigate the performance of relative enhancement on multiphasic MRI to differentiate clear cell renal cell carcinoma (RCC) from other RCC subtypes (papillary and chromophobe) and oncocytoma. MATERIALS AND METHODS: For this study, we derived a cohort of 34 clear cell RCCs, nine oncocytomas, 12 papillary RCCs, and 10 chromophobe RCCs with a preoperative multiphasic dynamic contrast-enhanced MRI study with up to four phases (i.e., unenhanced, corticomedullary, nephrographic, excretory) from 2005 to 2016. These groups were evaluated for multiphasic enhancement and were compared using Kruskal-Wallis and Mann-Whitney tests. ROC curves were constructed and logistic regression analyses were performed to evaluate the performance of multiphasic enhancement in differentiating clear cell RCCs from the other three groups.
April 2017
The Effect of Radiation Dose Reduction on Computer-Aided Detection (CAD) Performance in a Low-dose Lung Cancer Screening Population.PURPOSE: Lung cancer screening with low-dose CT has recently been approved for reimbursement, heralding the arrival of such screening services worldwide. Computer-aided detection (CAD) tools offer the potential to assist radiologists in detecting nodules in these screening exams. In lung screening, as in all CT exams, there is interest in further reducing radiation dose. However, the effects of continued dose reduction on CAD performance are not fully understood. In this work, we investigated the effect of reducing radiation dose on CAD lung nodule detection performance in a screening population. METHODS: The raw projection data files were collected from 481 patients who underwent low-dose screening CT exams at our institution as part of the National Lung Screening Trial (NLST). All scans were performed on a multidetector scanner (Sensation 64, Siemens Healthcare, Forchheim Germany) according to the NLST protocol, which called for a fixed tube current scan of 25 effective mAs for standard-sized patients and 40 effective mAs for larger patients. The raw projection data were input to a reduced-dose simulation software to create simulated reduced-dose scans corresponding to 50% and 25% of the original protocols. All raw data files were reconstructed at the scanner with 1 mm slice thickness and B50 kernel. The lungs were segmented semi-automatically, and all images and segmentations were input to an in-house CAD algorithm trained on higher dose scans (75-300 mAs). CAD findings were compared to a reference standard generated by an experienced reader. Nodule- and patient-level sensitivities were calculated along with false positives per scan, all of which were evaluated in terms of the relative change with respect to dose. Nodules were subdivided based on size and solidity into categories analogous to the LungRADS assessment categories, and sub-analyses were performed.
March 2017
Sympathetic Modulation of Electrical Activation in Normal and Infarcted Myocardium: Implications for Arrhythmogenesis.The influence of cardiac sympathetic innervation on electrical activation in normal and chronically infarcted ventricular myocardium is not understood. Yorkshire pigs with normal hearts (NL, n = 12) or anterior myocardial infarction (MI, n = 9) underwent high-resolution mapping of the anteroapical left ventricle at baseline and during left and right stellate ganglion stimulation (LSGS and RSGS, respectively). Conduction velocity (CV), activation times (ATs), and directionality of propagation were measured. Myocardial fiber orientation was determined using diffusion tensor imaging and histology. Longitudinal CV (CVL) was increased by RSGS (0.98 ± 0.11 vs. 1.2 ± 0.14m/s, P < 0.001) but not transverse CV (CVT). This increase was abrogated by β-adrenergic receptor and gap junction (GJ) blockade. Neither CVL nor CVT was increased by LSGS. In the peri-infarct region, both RSGS and LSGS shortened ARIs in sinus rhythm (423 ± 37 vs. 322 ± 30 ms, P < 0.001, and 423 ± 36 vs. 398 ± 36 ms, P = 0.035, respectively) and altered activation patterns in all animals. CV, as estimated by mean ATs, increased in a directionally dependent manner by RSGS (14.6 ± 1.2 vs. 17.3 ± 1.6 ms, P = 0.015), associated with GJ lateralization. RSGS and LSGS inhomogeneously modulated AT and induced relative or absolute functional activation delay in parts of the mapped regions in 75 and 67%, respectively, in MI animals, and in 0 and 15%, respectively, in control animals (P < 0.001 for both). In conclusion, sympathoexcitation increases CV in normal myocardium and modulates activation propagation in peri-infarcted ventricular myocardium. These data demonstrate functional control of arrhythmogenic peri-infarct substrates by sympathetic nerves and in part explain the temporal nature of arrhythmogenesis.NEW & NOTEWORTHY This study demonstrates regional control of conduction velocity in normal hearts by sympathetic nerves. In infarcted hearts, however, not only is modulation of propagation heterogeneous, some regions showed paradoxical conduction slowing. Sympathoexcitation altered propagation in all infarcted hearts studied, and we describe the temporal arrhythmogenic potential of these findings.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/sympathetic-nerves-and-cardiac-propagation/.
March 2017
Heads Up! A Novel Provocative Maneuver to Guide Acute Ischemic Stroke Management.BACKGROUND: A common dilemma in acute ischemic stroke management is whether to pursue recanalization therapy in patients with large vessel occlusions but minimal neurologic deficits. We describe and report preliminary experience with a provocative maneuver, i.e. 90-degree elevation of the head of bed for 30 min, which stresses collaterals and facilitates decision-making. METHODS: A prospective cohort study of <7.5 h of acute anterior circulation territory ischemia patients with minimal deficits despite middle cerebral artery (MCA) or internal carotid artery (ICA) occlusive disease.
March 2017
Combined Intravenous Thrombolysis and Thrombectomy vs Thrombectomy Alone for Acute Ischemic Stroke: A Pooled Analysis of the SWIFT and STAR Studies.Mechanical thrombectomy (MT) improves clinical outcomes in patients with acute ischemic stroke (AIS) caused by a large vessel occlusion. However, it is not known whether intravenous thrombolysis (IVT) is of added benefit in patients undergoing MT. OBJECTIVE: To examine whether treatment with IVT before MT with a stent retriever is beneficial in patients undergoing MT. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis used data from 291 patients treated with MT included in 2 large, multicenter, prospective clinical trials that evaluated MT for AIS (Solitaire With the Intention for Thrombectomy performed from January 1, 2010, through December 31, 2011, and Solitaire Flow Restoration Thrombectomy for Acute Revascularization from January 1, 2010, through December 31, 2012). An independent core laboratory scored the radiologic outcomes in each trial. INTERVENTIONS: Patients were treated with IVT with tissue plasminogen activator followed by MT (IVT and MT group) with the use of a stent retriever or MT with a stent retriever alone (MT group).
March 2017
Reduced Expiratory Flow Rate among Heavy Smokers Increases Lung Cancer Risk. Results from the National Lung Screening Trial-American College of Radiology Imaging Network Cohort.RATIONALE: Although epidemiological studies consistently show that chronic obstructive pulmonary disease is associated with an increased risk of lung cancer, debate exists as to whether there is a linear relationship between the severity of airflow limitation and lung cancer risk. OBJECTIVES: We examined this in a large, prospective study of older heavy smokers from the American College of Radiology Imaging Network subcohort of the National Lung Screening Trial (ACRIN). Airflow limitation was defined by prebronchodilator spirometry subgrouped according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4. METHODS: In the National Lung Screening Trial-ACRIN cohort of 18,473 screening participants, 6,436 had airflow limitation (35%) and 12,037 (65%) had no airflow limitation. From these groups, 758 lung cancer cases were prospectively identified. Participants with airflow limitation were stratified according to GOLD groups 1 (n = 1,607), 2 (n = 3,528), 3 (n = 1,083), and 4 (n = 211). Lung cancer incidence at study end (mean follow-up, 6.4 yr) was compared between the GOLD groups and those with no airflow limitation (referent group).
March 2017
Genomic Adequacy from Solid Tumor Core Needle Biopsies of ex Vivo Tissue and in Vivo Lung Masses: Prospective Study.Purpose To identify the variables and factors that affect the quantity and quality of nucleic acid yields from imaging-guided core needle biopsy. Materials and Methods This study was approved by the institutional review board and compliant with HIPAA. The authors prospectively obtained 232 biopsy specimens from 74 patients (177 ex vivo biopsy samples from surgically resected masses were obtained from 49 patients and 55 in vivo lung biopsy samples from computed tomographic [CT]-guided lung biopsies were obtained from 25 patients) and quantitatively measured DNA and RNA yields with respect to needle gauge, number of needle passes, and percentage of the needle core. RNA quality was also assessed. Significance of correlations among variables was assessed with analysis of variance followed by linear regression. Conditional probabilities were calculated for projected sample yields. Results The total nucleic acid yield increased with an increase in the number of needle passes or a decrease in needle gauge (two-way analysis of variance, P < .0001 for both). However, contrary to calculated differences in volume yields, the effect of needle gauge was markedly greater than the number of passes. For example, the use of an 18-gauge versus a 20-gauge biopsy needle resulted in a 4.8-5.7 times greater yield, whereas a double versus a single pass resulted in a 2.4-2.8 times greater yield for 18- versus 20-gauge needles, respectively. Ninety-eight of 184 samples (53%) had an RNA integrity number of at least 7 (out of a possible score of 10). Conclusion With regard to optimizing nucleic acid yields in CT-guided lung core needle biopsies used for genomic analysis, there should be a preference for using lower gauge needles over higher gauge needles with more passes.
March 2017
Evaluation of Encephaloduroarteriosynangiosis Efficacy Using Probabilistic Independent Component Analysis Applied to Dynamic Susceptibility Contrast Perfusion MRI.BACKGROUND AND PURPOSE: Indirect cerebral revascularization has been successfully used for treatment in Moyamoya disease and symptomatic intracranial atherosclerosis. While angiographic neovascularization has been demonstrated after surgery, measurements of local tissue perfusion are scarce and may not reflect the reported successful clinical outcomes. We investigated probabilistic independent component analysis and conventional perfusion parameters from DSC-MR imaging to measure postsurgical changes in tissue perfusion. MATERIALS AND METHODS: In this prospective study, 13 patients underwent unilateral indirect cerebral revascularization and DSC-MR imaging before and after surgery. Conventional perfusion parameters (relative cerebral blood volume, relative cerebral blood flow, and TTP) and probabilistic independent components that reflect the relative contributions of DSC signals consistent with arterial, capillary, and venous hemodynamics were calculated and examined for significant changes after surgery. Results were compared with postsurgical DSA studies to determine whether changes in tissue perfusion were due to postsurgical neovascularization.
March 2017
Effects of MRI Protocol Parameters, Preload Injection Dose, Fractionation Strategies, and Leakage Correction Algorithms on the Fidelity of Dynamic-Susceptibility Contrast MRI Estimates of Relative Cerebral Blood Volume in Gliomas.BACKGROUND AND PURPOSE: DSC perfusion MR imaging assumes that the contrast agent remains intravascular; thus, disruptions in the blood-brain barrier common in brain tumors can lead to errors in the estimation of relative CBV. Acquisition strategies, including the choice of flip angle, TE, TR, and preload dose and incubation time, along with post hoc leakage-correction algorithms, have been proposed as means for combating these leakage effects. In the current study, we used DSC-MR imaging simulations to examine the influence of these various acquisition parameters and leakage-correction strategies on the faithful estimation of CBV. MATERIALS AND METHODS: DSC-MR imaging simulations were performed in 250 tumors with perfusion characteristics randomly generated from the distributions of real tumor population data, and comparison of leakage-corrected CBV was performed with a theoretic curve with no permeability. Optimal strategies were determined by protocol with the lowest mean error.
March 2017
Bilateral Endolymphatic Hydrops in a Patient With Migraine Variant Without Vertigo: A Case Report.OBJECTIVE: To use modern high-resolution inner ear imaging modalities to evaluate for endolymphatic hydrops (EH) in a patient with migraine-associated fluctuating hearing loss without vertigo spells or dizziness. BACKGROUND: EH has been well described in patients with Meniere's disease on both human temporal bone studies and modern high-resolution imaging; however, there is no study to date, to our knowledge, that examines the presence of EH in a patient with migraine and bilateral hearing loss. We present the MRI findings using a sequence for detecting EH in a unique case of a patient experiencing migraine headaches accompanied by fluctuating hearing loss without vertigo. METHODS: Magnetic resonance imaging sequences included "cisternographic" three-dimensional T2, and delayed intravenous-enhanced three-dimensional fluid-attenuation inversion recovery (DIVE-3D-FLAIR) sequences, performed with 2350 ms (bright perilymph) and 2050 ms (bright endolymph) inversion times. The bright endolymph images were subtracted from bright perilymph images to create a composite image with bright perilymph, dark endolymph, and intermediate bone signals.
March 2017
Traumatic Hemorrhagic Brain Injury: Impact of Location and Resorption on Cognitive Outcome.OBJECTIVE Hemorrhagic contusions are often the most visible lesions following traumatic brain injury. However, the incidence, location, and natural history of traumatic parenchymal hemorrhage and its impact on neurological outcome have been understudied. The authors sought to examine the location and longitudinal evolution of traumatic parenchymal hemorrhage and its association with cognitive outcome. METHODS Sixteen patients with hemorrhagic contusions due to acceleration-deceleration injuries underwent MRI in the acute (mean 6.3 days postinjury) and chronic (mean 192.9 days postinjury) phases. ImageJ was used to generate GRE and FLAIR volumes. To account for the effect of head-size variability across individuals, the authors calculated each patient's total brain tissue volume using SIENAX. GRE and FLAIR volumes were normalized to the total brain tissue volume, and values for absolute and percent lesion volume and total brain volume change were generated. Spearman's rank correlations were computed to determine associations between neuroimaging and 6-month postinjury neuropsychological testing of attention (Symbol Digit Modalities Test [SDMT], oral [O] and written [W] versions), memory (Selective Reminding Test, total learning and delayed recall), and executive function (Trail Making Test Part B [TMT-B]). RESULTS The patients' mean age was 31.4 ± 14.0 years and their mean Glasgow Coma Scale score at admission was 7.9 ± 2.8. Lesions were predominantly localized to the frontal (11 lesions) and temporal (9 lesions) lobes. The average percent reductions in GRE and FLAIR volumes were 44.2% ± 46.1% and 80.5% ± 26.3%, respectively. While total brain and frontal lesion volumes did not correlate with brain atrophy, larger temporal lobe GRE and FLAIR volumes were associated with larger volumes of atrophy (GRE: acute, -0.87, p < 0.01, chronic, -0.78, p < 0.01; FLAIR: acute, -0.81, p < 0.01, chronic, -0.88, p < 0.01). Total percent volume change of GRE lesions correlated with TMT-B (0.53, p < 0.05) and SDMT-O (0.62, p < 0.05) scores. Frontal lobe lesion volume did not correlate with neuropsychological outcome. However, robust relationships were seen in the temporal lobe, with larger acute temporal lobe GRE volumes were associated with worse scores on both oral and written versions of the SDMT (SDMT-W, -0.85, p < 0.01; SDMT-O, -0.73, p < 0.05). Larger absolute change in temporal GRE volume was strongly associated with worse SDMT scores (SDMT-W, 0.88, p < 0.01; SDMT-O, 0.75, p < 0.05). The same relationships were also seen between temporal FLAIR lesion volumes and neuropsychological outcome. CONCLUSIONS Traumatic parenchymal hemorrhages are largely clustered in the frontal and temporal lobes, and significant residual blood products are present at 6 months postinjury, a potential source of ongoing secondary brain injury. Neuropsychological outcome is closely tied to lesion volume size, particularly in the temporal lobe, where larger GRE and FLAIR volumes are associated with more brain atrophy and worse SDMT scores. Interestingly, larger volumes of hemorrhage resorption were associated with worse SDMT and TMT-B scores, suggesting that the initial tissue damage had a lasting impact on attention and executive function.
March 2017
Targeted Biopsy to Detect Gleason Score Upgrading during Active Surveillance for Men with Low versus Intermediate Risk Prostate Cancer.PURPOSE: We sought to determine the rate of upgrading to Gleason score 4 + 3 or greater using targeted biopsy for diagnosis and monitoring in men undergoing active surveillance of prostate cancer. MATERIALS AND METHODS: Study subjects comprised all 259 men, including 196 with Gleason score 3 + 3 and 63 with Gleason score 3 + 4, who were diagnosed by magnetic resonance imaging/ultrasound fusion guided biopsy from 2009 to 2015 and underwent subsequent fusion biopsy for as long as 4 years of active surveillance. The primary end point was the discovery of Gleason score 4 + 3 or greater prostate cancer. Followup biopsies included targeting of positive sites, which were tracked in an Artemis™ device. Kaplan-Meier curves were generated to determine upgrading rates, stratified by initial Gleason score and prostate specific antigen density.
March 2017
Human TERT Promoter Mutation Enables Survival Advantage from MGMT Promoter Methylation in IDH1 Wild-type Primary Glioblastoma Treated by Standard Chemoradiotherapy.BACKGROUND: Promoter mutation in the human telomerase reverse transcriptase gene (hTERT) occurs in ~75% of primary glioblastoma (GBM). Although the mutation appears to upregulate telomerase expression and contributes to the maintenance of telomere length, its clinical significance remains unclear. METHODS: We performed hTERT promoter genotyping on 303 isocitrate dehydrogenase 1 wild-type GBM tumors treated with standard chemoradiotherapy. We also stratified 190 GBM patients from the database of The Cancer Genome Atlas (TCGA) by hTERT gene expression. We analyzed overall and progression-free survival by Kaplan-Meier and Cox regression.
March 2017
MRI with Ferumoxytol: A Single Center Experience of Safety Across the Age Spectrum.PURPOSE: To summarize our single-center safety experience with the off-label use of ferumoxytol for magnetic resonance imaging (MRI) and to compare the effects of ferumoxytol on monitored physiologic indices in patients under anesthesia with those of gadofosveset trisodium. MATERIALS AND METHODS: Consecutive patients who underwent ferumoxytol-enhanced (FE) MRI exams were included. Adverse events (AEs) were classified according to the Common Terminology Criteria for Adverse Events v4.0. In a subgroup of patients examined under general anesthesia, recording of blood pressure, heart rate, oxygen saturation, and end-tidal CO2 was performed. A comparable group of 23 patients who underwent gadofosveset-enhanced (GE) MRI under anesthesia with similar monitoring was also analyzed.
March 2017
Longterm Follow-up of Small Pancreatic Cystic Lesions in Liver Transplant Recipients.Incidental small pancreatic cystic lesions (PCLs) are often found on preoperative imaging in patients undergoing orthotopic liver transplantation (OLT). Although these are considered benign or of low malignant potential, the influence of immunosuppression after OLT may be of concern. The aim of this study was to observe the longterm outcome of these small PCLs in post-OLT patients. An institutional OLT database of 1778 consecutive OLT patients from January 2000 to December 2010 was analyzed. Computed tomography, magnetic resonance imaging, or endoscopic ultrasound at the time of OLT and all subsequent imaging, cytology, fluid analysis of PCLs, and patient status were evaluated. A total of 70 patients with 182 PCLs, of benign or low malignant potential, were identified with a mean follow-up time of 64 months. At initial diagnosis of PCLs in 48 patients, 7 branch duct-type intraductal papillary mucinous neoplasms (B-IPMNs), 1 serous cystadenoma (SCA), and 40 nonspecific benign cysts were identified. Final diagnosis at the end of the follow-up revealed 16 B-IPMNs, 3 SCAs, and a mixed acinar-neuroendocrine carcinoma, in which the latter developed 9 years after initial diagnosis of B-IPMN. During the follow-up time, average increase in size and number of PCLs were 4.5 mm and 1.4, respectively (P < 0.001 for both). The majority of incidental PCLs in OLT patients showed an indolent behavior despite immunosuppression. Risk of malignancy development was very low and comparable with normal population.
February 2017
Percutaneous Cryoablation for the Treatment of Recurrent Malignant Pleural Mesothelioma: Safety, Early-Term Efficacy, and Predictors of Local Recurrence.PURPOSE: To determine safety and early-term efficacy of CT-guided cryoablation for treatment of recurrent mesothelioma and assess risk factors for local recurrence. MATERIALS AND METHODS: During the period 2008-2012, 24 patients underwent 110 cryoablations for recurrent mesothelioma tumors in 89 sessions. Median patient age was 69 years (range, 48-82 y). Median tumor size was 30 mm (range, 9-113 mm). Complications were graded using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Recurrence was diagnosed on CT or positron emission tomography/CT by increasing size, nodular enhancement, or hypermetabolic activity and analyzed using the Kaplan-Meier method. Cox proportional hazards model was used to determine covariates associated with local tumor recurrence.
February 2017
Light-sheet Fluorescence Imaging to Localize Cardiac Lineage and Protein Distribution.Light-sheet fluorescence microscopy (LSFM) serves to advance developmental research and regenerative medicine. Coupled with the paralleled advances in fluorescence-friendly tissue clearing technique, our cardiac LSFM enables dual-sided illumination to rapidly uncover the architecture of murine hearts over 10 by 10 by 10 mm3 in volume; thereby allowing for localizing progenitor differentiation to the cardiomyocyte lineage and AAV9-mediated expression of exogenous transmembrane potassium channels with high contrast and resolution. Without the steps of stitching image columns, pivoting the light-sheet and sectioning the heart mechanically, we establish a holistic strategy for 3-dimentional reconstruction of the "digital murine heart" to assess aberrant cardiac structures as well as the spatial distribution of the cardiac lineages in neonates and ion-channels in adults.
February 2017
Prostate Artery Embolization for Benign Prostatic Hyperplasia: Current Status.Prostate artery embolization has garnered much attention as a promising treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia. We aim to provide an up-to-date review of this minimally invasive technique, including discussion of potential benefits and technical challenges. Current evidence suggests it is a safe and effective option for patients with medication-refractory urinary obstructive symptoms who are poor surgical candidates or refuse surgical therapy. Larger, randomized studies with long-term follow-up data are needed for this technique to be formally established in the treatment paradigm for benign prostatic hyperplasia.
February 2017
Radiographic and Magnetic Resonance Imaging Identification of Thoracolumbar Spine Variants with Implications for the Positioning of the Conus Medullaris in Rhesus Macaques.The anatomy of the vertebral column in mammals may differ between species and between subjects of the same species, especially with regards to the composition of the thoracolumbar spine. We investigated, using several noninvasive imaging techniques, the thoracolumbar spine of a total of 44 adult rhesus macaques of both genders. Radiographic examination of the vertebral column showed a predominant spine phenotype with 12 rib-bearing thoracic vertebrae and 7 lumbar vertebrae without ribs in 82% of subjects, whereas a subset of subjects demonstrated 13 rib-bearing thoracic vertebrae and 6 lumbar vertebrae without ribs. Computer tomography studies of the thoraco-lumbar spine in two cases with a pair of supernumerary ribs showed facet joints between the most caudal pair of ribs and the associated vertebra, supporting a thoracic phenotype. Magnetic resonance imaging (MRI) studies were used to determine the relationship between the lumbosacral spinal cord and the vertebral column. The length of the conus medullaris portion of the spinal cord was 1.5 ± 0.3 vertebral units, and its rostral and caudal positions in the spinal canal were at 2.0 ± 0.3 and 3.6 ± 0.4 vertebral units below the thoracolumbar junction, respectively (n = 44). The presence of a set of supernumerary ribs did not affect the length or craniocaudal position of the conus medullaris, and subjects with13 rib-bearing vertebrae may from a functional or spine surgical perspective be considered as exhibiting12 thoracic vertebrae and an L1 vertebra with ribs.
February 2017
Bone Age and Mineral Density Assessments Using Plain Roentgenograms in Tenofovir-exposed Infants in Malawi and Brazil Enrolled in HIV Prevention Trials Network 057.BACKGROUND: Tenofovir disoproxil fumarate (TDF) use during pregnancy has been increasing, and studies linking bone toxicity with exposure to TDF have raised concern for its use in infants. METHODS: Hand/wrist and spine radiographs were obtained at 3 days and 12 weeks of age in infants born to HIV-infected pregnant women enrolled in the HIV Prevention Trials Network 057 pharmacokinetic study of TDF conducted in Malawi and Brazil assigned to 3 TDF dosing cohorts. In cohort 1, mothers received 600 mg of TDF during labor. In cohort 2, infants received 4 mg/kg dose on days 0, 3 and 5. In cohort 3, a 900 mg maternal dose was given during labor, followed by a 6 mg/kg infant dose on days 0, 3 and 5 of life.
February 2017
Magnetic Resonance Imaging Underestimation of Prostate Cancer Geometry: Use of Patient Specific Molds to Correlate Images with Whole Mount Pathology.PURPOSE: We evaluated the accuracy of magnetic resonance imaging in determining the size and shape of localized prostate cancer. MATERIALS AND METHODS: The subjects were 114 men who underwent multiparametric magnetic resonance imaging before radical prostatectomy with patient specific mold processing of the specimen from 2013 to 2015. T2-weighted images were used to contour the prostate capsule and cancer suspicious regions of interest. The contours were used to design and print 3-dimensional custom molds, which permitted alignment of excised prostates with magnetic resonance imaging scans. Tumors were reconstructed in 3 dimensions from digitized whole mount sections. Tumors were then matched with regions of interest and the relative geometries were compared.
February 2017
A Bayesian Model for Estimating Multi-state Disease Progression.A growing number of individuals who are considered at high risk of cancer are now routinely undergoing population screening. However, noted harms such as radiation exposure, overdiagnosis, and overtreatment underscore the need for better temporal models that predict who should be screened and at what frequency. The mean sojourn time (MST), an average duration period when a tumor can be detected by imaging but with no observable clinical symptoms, is a critical variable for formulating screening policy. Estimation of MST has been long studied using continuous Markov model (CMM) with Maximum likelihood estimation (MLE). However, a lot of traditional methods assume no observation error of the imaging data, which is unlikely and can bias the estimation of the MST. In addition, the MLE may not be stably estimated when data is sparse. Addressing these shortcomings, we present a probabilistic modeling approach for periodic cancer screening data. We first model the cancer state transition using a three state CMM model, while simultaneously considering observation error. We then jointly estimate the MST and observation error within a Bayesian framework. We also consider the inclusion of covariates to estimate individualized rates of disease progression. Our approach is demonstrated on participants who underwent chest x-ray screening in the National Lung Screening Trial (NLST) and validated using posterior predictive p-values and Pearson's chi-square test. Our model demonstrates more accurate and sensible estimates of MST in comparison to MLE.
January 2017
Baseline Pretreatment Contrast Enhancing Tumor Volume Including Central Necrosis is a Prognostic Factor in Recurrent Glioblastoma: Evidence from Single and Multicenter Trials.BACKGROUND: The prognostic significance of baseline contrast enhancing tumor prior to second- or third-line therapy in recurrent glioblastoma (GBM) for overall survival (OS) remains controversial, particularly in the context of repeated surgical resection and/or use of anti-angiogenic therapy. In the current study, we examined recurrent GBM patients from both single and multicenter clinical trials to test whether baseline enhancing tumor volume, including central necrosis, is a significant prognostic factor for OS in recurrent GBM. METHODS: Included were 497 patients with recurrent GBM from 4 data sources: 2 single-center sites (University of Toronto, University of California Los Angeles) and 2 phase II multicenter trials (AVF3708G, Bevacizumab ± Irinotecan, NCT00345163; XL184-201, Cabozantinib, NCT00704288). T1 subtraction maps were used to define volume of contrast enhancing tumor, including central necrosis. Cox multivariable and univariate analyses were used to evaluate the relationship between tumor volume prior to second- or third-line therapy and OS.
January 2017
Patient Size-Specific Analysis of Dose Indexes From CT Lung Cancer Screening.OBJECTIVE: The U.S. Centers for Medicare & Medicaid Services (CMS) recently approved the use of low-dose CT for lung cancer screening and described volumetric CT dose index (CTDIvol) requirements. These were based on the National Lung Screening Trial, which used only fixed-tube-current techniques. The aim of this study was to evaluate dose index data from a lung cancer screening program using automatic exposure control (AEC) techniques to ensure compliance with requirements and to correlate dose index values with patient size. MATERIALS AND METHODS: CTDIvol, dose-length product (DLP), and body mass index (BMI) data were collected for 563 lung cancer screening examinations performed with AEC between January 1, 2014, through August 31, 2015. CTDIvol and DLP were analyzed according to the patient's BMI classification. Results were compared with the CMS requirement that the CTDIvol for a standard-sized patient (height, 170 cm; weight, 70 kg) be 3.0 mGy or less, with adjustments for patients of different sizes. For a subset of patients, the average water-equivalent diameter and size-specific dose estimate were estimated.
January 2017
Percutaneous Lung Biopsy in the Molecular Profiling Era: A Survey of Current Practices.PURPOSE: This study aimed to assess the current practice patterns of radiologists performing percutaneous lung biopsies. MATERIALS AND METHODS: This cross-sectional study used a web-based survey sent to the Society of Thoracic Radiology membership from August to October 2015. Responses were collected anonymously, and results were tallied.
January 2017
Multi-delay ASL Can Identify Leptomeningeal Collateral Perfusion in Endovascular Therapy of Ischemic Stroke.BACKGROUND AND PURPOSE: Multi-delay arterial spin-labeling (ASL) perfusion imaging has been used as a promising modality to evaluate cerebral perfusion. Our aim was to assess the association of leptomeningeal collateral perfusion scores based on ASL parameters with outcome of endovascular treatment in patients with acute ischemic stroke (AIS) in the middle cerebral artery (MCA) territory. MATERIALS AND METHODS: ASL data at 4 post-labeling delay (PLD) times (PLD = 1.5, 2, 2.5, 3 s) were acquired during routine clinical magnetic resonance examination on AIS patients prior to endovascular treatment. A 3-point scale of leptomeningeal collateral perfusion grade on 10 anatomic regions was determined based on arterial transit times (ATT), cerebral blood flow (CBF), and arterial cerebral blood volume (CBV), estimated by the multi-delay ASL protocol. Based on a 90-day modified Rankin Scale (mRS), the patients were dichotomized to moderate/good (mRS 0-3) and poor outcome (mRS 4-6) and the regional collateral flow scores were compared.
January 2017
Utilization of Emergent Neuroimaging for Thrombolysis-Eligible Stroke Patients.BACKGROUND: Advances in diagnostic imaging of stroke include multimodal techniques such as noninvasive angiography and perfusion imaging. We aimed to characterize trends in neuroimaging utilization among acute stroke patients. Utilization of multimodal imaging for acute stroke in the community has remained largely uncharacterized despite its increased adoption at academic medical centers. METHODS: We quantified neuroimaging utilization in the emergency department (ED) for 1,700 hyperacute stroke patients presenting <2 hours after symptom onset who participated in the National Institutes of Health Field Administration of Stroke Therapy-Magnesium (FAST-MAG) study throughout Los Angeles and Orange Counties. FAST-MAG provided no recommendation as to imaging utilization.
January 2017
Evaluating Small-Airways Disease in Asthmatic Patients: The Utility of Quantitative Computed Tomography.The tracheobronchial tree comprises a branching system of airways, beginning with the trachea, in which each airway divides mostly dichotomously into 2 smaller airways of progressively smaller diameter and, in most cases, shorter length, down to the smallest airway (a respiratory bronchiole) before terminating after approximately 23 divisions in the distal air sacs and alveoli. Historically, the lower respiratory tract has been divided into large and small airways, the latter defined as airways of 2 mm in diameter or smaller and corresponding to approximately the seventh or eighth generation and beyond of branching airways. In view of the exponential increase in the number of airways with each successive generation, most of the tracheobronchial tree is comprised of small airways, the total cross-sectional area of which is much greater than that of the larger airways, resulting in a relatively low resistance to airflow in the healthy lung.
January 2017
Clear Cell Renal Cell Carcinoma: Identifying the Gain of Chromosome 12 on Multiphasic MDCT.PURPOSE: To determine whether multiphasic MDCT enhancement can help identify the gain of chromosome 12 in clear cell renal cell carcinomas (RCCs). METHODS: With IRB approval for this HIPAA-compliant case control study, we derived a cohort of 65 clear cell RCCs with preoperative four-phase renal mass MDCT from October 2000 to August 2013. Each lesion was segmented in its entirety on axial images in all phases. A computer-assisted detection (CAD) algorithm selected a 0.5-cm-diameter region of maximal attenuation within each lesion in each phase. Attenuation in each phase between clear cell RCCs with and without the gain of 12 was compared using t-tests.
