Nicholas T. Befera

Anatomical and functional imaging of myocardial infarction in mice using micro‐CT and eXIA 160 contrast agent

Noninvasive small animal imaging techniques are essential for evaluation of cardiac disease and potential therapeutics. A novel preclinical iodinated contrast agent called eXIA 160 has recently been developed, which has been evaluated for micro-CT cardiac imaging. eXIA 160 creates strong contrast between blood and tissue immediately after its injection and is subsequently taken up by the myocardium and other metabolically active tissues over time. We focus on these properties of eXIA and show its use in imaging myocardial infarction in mice. Five C57BL/6 mice were imaged ~2 weeks after left anterior descending coronary artery ligation. Six C57BL/6 mice were used as controls. Immediately after injection of eXIA 160, an enhancement difference between blood and myocardium of ~340 HU enabled cardiac function estimation via 4D micro-CT scanning with retrospective gating. Four hours post-injection, the healthy perfused myocardium had a contrast difference of ~140 HU relative to blood while the infarcted myocardium showed no enhancement. These differences allowed quantification of infarct size via dual-energy micro-CT. In vivo micro-SPECT imaging and ex vivo triphenyl tetrazolium chloride (TTC) staining provided validation for the micro-CT findings. Root mean squared error of infarct measurements was 2.7% between micro-CT and SPECT, and 4.7% between micro-CT and TTC. Thus, micro-CT with eXIA 160 can be used to provide both morphological and functional data for preclinical studies evaluating myocardial infarction and potential therapies. Further studies are warranted to study the potential use of eXIA 160 as a CT molecular imaging tool for other metabolically active tissues in the mouse.

Assessing Cardiac Injury in Mice With Dual Energy-MicroCT, 4D-MicroCT, and MicroSPECT Imaging After Partial Heart Irradiation

PURPOSE To develop a mouse model of cardiac injury after partial heart irradiation (PHI) and to test whether dual energy (DE)-microCT and 4-dimensional (4D)-microCT can be used to assess cardiac injury after PHI to complement myocardial perfusion imaging using micro-single photon emission computed tomography (SPECT). METHODS AND MATERIALS To study cardiac injury from tangent field irradiation in mice, we used a small-field biological irradiator to deliver a single dose of 12 Gy x-rays to approximately one-third of the left ventricle (LV) of Tie2Cre; p53(FL/+) and Tie2Cre; p53(FL/-) mice, where 1 or both alleles of p53 are deleted in endothelial cells. Four and 8 weeks after irradiation, mice were injected with gold and iodinated nanoparticle-based contrast agents, and imaged with DE-microCT and 4D-microCT to evaluate myocardial vascular permeability and cardiac function, respectively. Additionally, the same mice were imaged with microSPECT to assess myocardial perfusion. RESULTS After PHI with tangent fields, DE-microCT scans showed a time-dependent increase in accumulation of gold nanoparticles (AuNp) in the myocardium of Tie2Cre; p53(FL/-) mice. In Tie2Cre; p53(FL/-) mice, extravasation of AuNp was observed within the irradiated LV, whereas in the myocardium of Tie2Cre; p53(FL/+) mice, AuNp were restricted to blood vessels. In addition, data from DE-microCT and microSPECT showed a linear correlation (R(2) = 0.97) between the fraction of the LV that accumulated AuNp and the fraction of LV with a perfusion defect. Furthermore, 4D-microCT scans demonstrated that PHI caused a markedly decreased ejection fraction, and higher end-diastolic and end-systolic volumes, to develop in Tie2Cre; p53(FL/-) mice, which were associated with compensatory cardiac hypertrophy of the heart that was not irradiated. CONCLUSIONS Our results show that DE-microCT and 4D-microCT with nanoparticle-based contrast agents are novel imaging approaches complementary to microSPECT for noninvasive assessment of the change in myocardial vascular permeability and cardiac function of mice in whom myocardial injury develops after PHI.

A high-resolution cardiovascular magnetic resonance diffusion tensor map from ex-vivo C57BL/6 murine hearts

BackgroundThe complex cardiac fiber structural organization and spatial arrangement of cardiomyocytes in laminar sheetlets contributes greatly to cardiac functional and contractile ejection patterns. This study presents the first comprehensive, ultra-high resolution, fully quantitative statistical tensor map of the fixed murine heart at isotropic resolution of 43 μm using diffusion tensor (DT) cardiovascular magnetic resonance (CMR).MethodsImaging was completed in approximately 12 hours using a six-directional encoding scheme, in five ex vivo healthy C57BL/6 mouse hearts. The tensor map constructed from this data provides an average description of the murine fiber architecture visualized with fiber tractography, and its population variability, using the latest advances in image tensor analysis and statistics.ResultsResults show that non-normalized cardiac tensor maps are associated with mean fractional anisotropy of 0.25 ± 0.07 and mean diffusivity of 8.9 ± 1.6 × 10−4 mm2/s. Moreover, average mid-ventricular helical angle distributions ranged between –41 ± 3° and +52 ± 5° and were highly correlated with transmural depth, in agreement with prior published results in humans and canines. Calculated variabilities of local myocyte orientations were 2.0° and 1.4°. Laminar sheet orientation variability was found to be less stable at 2.6°. Despite such variations, the murine heart seems to be highly structured, particularly when compared to canines and humans.ConclusionsThis tensor map has the potential to yield an accurate mean representation and identification of common or unique features of the cardiac myocyte architecture, to establish a baseline standard reference of DTI indices, and to improve detection of biomarkers, especially in pathological states or post-transgenetic modifications.

Abdominopelvic and Lower Extremity Deep Venous Thrombosis: Evaluation With Contrast-Enhanced MR Venography With a Blood-Pool Agent

OBJECTIVE The purpose of this article is to evaluate contrast-enhanced (CE) MR venography (MRV) with a blood-pool agent for detection of abdominopelvic and lower extremity deep venous thrombosis (DVT) compared with a conventional unenhanced gradient-recalled echo (GRE) MRV technique. MATERIALS AND METHODS This retrospective study was performed on 30 patients (mean age, 52.7 years; 15 men and 15 women) referred for MRV between March 2010 and November 2010 for evaluation of lower extremity or abdominopelvic DVT. All patients underwent a GRE sequence followed by a CE T1-weighted sequence with gadofosveset, a blood-pool agent. The abdominopelvic and lower extremity venous system was divided into 13 segments. The presence of acute or chronic DVT was assessed by six radiologists, as well as qualitative and quantitative assessments of each venous segment. Image acquisition and interpretation times were also tabulated. RESULTS The sensitivity and specificity for acute DVT were 91.0% and 99.8%, respectively, on CE MRV compared with 80.8% and 95.8%, respectively, on GRE MRV (p = 0.077 and p < 0.001). The sensitivity and specificity for chronic DVT were 84.4% and 98.4%, respectively, on CE MRV and 64.5% and 95.6%, respectively, on GRE MRV (p < 0.001 for both). Subjective ratings of vein visualization, signal homogeneity, and confidence pertaining to DVT diagnosis were significantly higher with the CE images (p < 0.001). The contrast-to-noise ratio for CE images was similar or significantly higher for all venous segments. Image acquisition and radiologist interpretation times on the CE studies were decreased (p < 0.001). CONCLUSION Gadofosveset-enhanced MRV had equal or higher sensitivity and specificity for detection of DVT than did GRE MRV, with decreased time for image acquisition and interpretation.

Performance of a Machine Learning Classifier of Knee MRI Reports in Two Large Academic Radiology Practices: A Tool to Estimate Diagnostic Yield

OBJECTIVE The purpose of this study is to evaluate the performance of a natural language processing (NLP) system in classifying a database of free-text knee MRI reports at two separate academic radiology practices. MATERIALS AND METHODS An NLP system that uses terms and patterns in manually classified narrative knee MRI reports was constructed. The NLP system was trained and tested on expert-classified knee MRI reports from two major health care organizations. Radiology reports were modeled in the training set as vectors, and a support vector machine framework was used to train the classifier. A separate test set from each organization was used to evaluate the performance of the system. We evaluated the performance of the system both within and across organizations. Standard evaluation metrics, such as accuracy, precision, recall, and F1 score (i.e., the weighted average of the precision and recall), and their respective 95% CIs were used to measure the efficacy of our classification system. RESULTS The accuracy for radiology reports that belonged to the models clinically significant concept classes after training data from the same institution was good, yielding an F1 score greater than 90% (95% CI, 84.6-97.3%). Performance of the classifier on cross-institutional application without institution-specific training data yielded F1 scores of 77.6% (95% CI, 69.5-85.7%) and 90.2% (95% CI, 84.5-95.9%) at the two organizations studied. CONCLUSION The results show excellent accuracy by the NLP machine learning classifier in classifying free-text knee MRI reports, supporting the institution-independent reproducibility of knee MRI report classification. Furthermore, the machine learning classifier performed well on free-text knee MRI reports from another institution. These data support the feasibility of multiinstitutional classification of radiologic imaging text reports with a single machine learning classifier without requiring institution-specific training data.

CT Fluoroscopy–Guided Blood Patching of Ventral CSF Leaks by Direct Needle Placement in the Ventral Epidural Space Using a Transforaminal Approach

BACKGROUND AND PURPOSE: Epidural blood patch treatment of spontaneous intracranial hypotension arising from ventral CSF leaks can be difficult secondary to challenges in achieving ventral spread of patching material. The purpose of this study was to determine the technical success rates and safety profile of direct needle placement into the ventral epidural space via a posterior transforaminal approach. MATERIALS AND METHODS: We retrospectively reviewed consecutive CT fluoroscopy–guided epidural blood patches from June 2013 through July 2015. Cases were included if a posterior transforaminal approach was taken to place the needle directly in the ventral epidural space. Rates of technical success (defined as contrast in the spinal canal ventral epidural space) and optimal epidurogram (defined as contrast spreading into or beyond the middle third of the spinal canal ventral epidural space) were determined. Factors influencing these rates were assessed. All complications, inadvertent intravascular injections, and intrathecal punctures were recorded. RESULTS: A total of 72 ventral epidural blood patches were identified; immediate technical success was achieved in 95.8% and an optimal epidurogram in 47.2%. Needle position within the spinal canal ventral epidural space was associated with obtaining an optimal epidurogram (P = .005). Inadvertent intravascular injection was identified in 29.3% of cases, but all were venous. There were no inadvertent intrathecal punctures or complications. CONCLUSIONS: Direct needle placement in the ventral epidural space via a transforaminal approach for treatment of ventral CSF leaks has an excellent technical success rate and safety profile. This technique can be considered as a treatment option in selected patients with ventral CSF leaks for whom traditional techniques are unsuccessful.

Physician Self-Referral and Imaging Use Appropriateness: Negative Cervical Spine MRI Frequency as an Assessment Metric

Five hundred cervical spine MRI studies,half ordered by referring physicians who owned scanners and received technical fees and half by physicians who did not, were reviewed for percentage of negative results and number of concomitant shoulder MRIs performed. There were 17.3% more negative scans in the financial-interest group. Patients in this group were also more likely to undergo shoulder MRI. BACKGROUND AND PURPOSE: Imaging self-referral is increasingly cited as a contributor to diagnostic imaging overuse. The purpose of this study was to determine whether ownership of MR imaging equipment by ordering physicians influences the frequency of negative cervical spine MR imaging findings. MATERIALS AND METHODS: A retrospective review was performed of 500 consecutive cervical spine MRIs ordered by 2 separate referring-physician groups serving the same geographic community. The first group owned the scanners used and received technical fees for their use, while the second group did not. Final reports were reviewed, and for each group, the percentage of negative study findings and the frequency of abnormalities were calculated. The number of concomitant shoulder MRIs was recorded. RESULTS: Five hundred MRIs meeting inclusion criteria were reviewed (250 with financial interest, 250 with no financial interest). Three hundred fifty-two had negative findings (190 with financial interest, 162 with no financial interest); there were 17.3% more scans with negative findings in the financial interest group (P = .006). Among scans with positive findings, there was no significant difference in the mean number of lesions per scan, controlled for age (1.90 with financial interest, 2.19 with no financial interest; P = .23). Patients in the financial interest group were more likely to undergo concomitant shoulder MR imaging (24 with financial interest, 11 with no financial interest; P = .02). CONCLUSIONS: Cervical spine MRIs referred by physicians with a financial interest in the imaging equipment used were significantly more likely to have negative findings. There was otherwise a highly similar distribution and severity of disease between the 2 patient samples. Patients in the financial interest group were more likely to undergo concomitant shoulder MR imaging.

Dual-energy micro-CT imaging of pulmonary airway obstruction: correlation with micro-SPECT

To match recent clinical dual energy (DE) CT studies focusing on the lung, similar developments for DE micro-CT of the rodent lung are required. Our group has been actively engaged in designing pulmonary gating techniques for micro- CT, and has also introduced the first DE micro-CT imaging method of the rodent lung. The aim of this study was to assess the feasibility of DE micro-CT imaging for the evaluation of airway obstruction in mice, and to compare the method with micro single photon emission computed tomography (micro-SPECT) using technetium-99m labeled macroaggregated albumin (99mTc-MAA). The results suggest that the induced pulmonary airway obstruction causes either atelectasis, or air-trapping similar to asthma or chronic bronchitis. Atelectasis could only be detected at early time points in DE micro-CT images, and is associated with a large increase in blood fraction and decrease in air fraction. Air trapping had an opposite effect with larger air fraction and decreased blood fraction shown by DE micro-CT. The decrease in perfusion to the hypoventilated lung (hypoxic vasoconstriction) is also seen in micro-SPECT. The proposed DE micro-CT technique for imaging localized airway obstruction performed well in our evaluation, and provides a higher resolution compared to micro-SPECT. Both DE micro-CT and micro-SPECT provide critical, quantitative lung biomarkers for image-based anatomical and functional information in the small animal. The methods are readily linked to clinical methods allowing direct comparison of preclinical and clinical results.

Onyx embolization of a pial AV fistula with a giant venous varix using a flow-directed Scepter balloon catheter: Technical note

Background and importance Pial arteriovenous fistulas (AVFs) of the brain are treacherous lesions that can be challenging to treat because of high risk of hemorrhage. We report on a rare case of a pial AVF with a giant venous varix as a draining vein treated successfully with flow-directed balloon-assisted Onyx embolization. Clinical presentation A 56-year-old female with headaches underwent brain magnetic resonance imaging, which demonstrated a 4 cm aneurysmal malformation in the right temporal lobe. A diagnostic cerebral angiogram demonstrated a right temporal pial AVF fed by an enlarged right posterior cerebral artery with drainage into a giant venous varix. Onyx embolization was curative using a flow-directed Scepter balloon catheter. Conclusion Flow-directed balloon-assisted Onyx embolization can be highly successful for the curative embolization of pial AVFs. Balloon application changes the nature of the lesion from high-flow–high risk to no-flow–low-risk. Using a flow-directed technique with balloon microcatheters may help minimize the risk of intracranial vascular injury.

Endovascular repair of an acute symptomatic carotid artery dissection through the false dissecting carotid lumen

A 48-year-old woman presented with an acute ischemic stroke (National Institutes of Health Stroke Scale (NIHSS) 21) six hours after symptom onset. Workup revealed a left cervical internal carotid artery (ICA) occlusive dissection, which was emergently reconstructed with a flow-diverting stent. A routine Duplex scan one hour later suggested reocclusion of the ICA, confirmed by angiography. The true lumen of the ICA could not be accessed and therefore the “false lumen” of the ICA dissection was entered proximally. The true lumen and ultimately the flow-diverting stent were accessed via the false lumen. In analogy to the subintimal arterial flossing with antegrade-retrograde intervention technique described for peripheral vascular disease, several stents were placed in telescoping fashion from the true common carotid lumen through the “false dissecting” lumen of the proximal ICA into the distal true lumen. The stent construct remained patent, and the patient recovered clinically to an NIHSS of 1.