Magnetic resonance elastography to estimate brain stiffness: Measurement reproducibility and its estimate in pseudotumor cerebri patients.

This study determines the reproducibility of magnetic resonance elastography (MRE) derived brain stiffness in normal volunteers and compares it against pseudotumor patients before and after lumbar puncture (LP). MRE was performed on 10 normal volunteers for reproducibility and 14 pseudotumor patients before and after LP. During LP, opening and closing cerebrospinal fluid (CSF) pressures were recorded before and after removal of CSF and correlated to brain stiffness. Stiffness reproducibility was observed (r > 0.78; p < 0.008). Whole brain opening LP stiffness was significantly (p = 0.04) higher than normals, but no significant difference (p = 0.11) in closing LP measurements. No significant correlation was observed between opening and closing pressure and brain stiffness.

Quantification of myocardial stiffness using magnetic resonance elastography in right ventricular hypertrophy: initial feasibility in dogs.

INTRODUCTION: Myocardial stiffness is an important determinant of cardiac function and is currently invasively and indirectly assessed by catheter angiography. This study aims to demonstrate the feasibility of quantifying right ventricular (RV) stiffness noninvasively using cardiac magnetic resonance elastography (CMRE) in dogs with severe congenital pulmonary valve stenosis (PVS) causing RV hypertrophy, and compare it to remote myocardium in the left ventricle (LV). Additionally, correlations between stiffness and selected pathophysiologic indicators from transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging were explored. METHODS: In-vivo CMRE was performed on nine dogs presenting severe congenital PVS using a 1.5T MRI scanner. T1-MOLLI, T2-prepared-bSSFP, gated-cine GRE-MRE and LGE (PSIR) sequences were used to acquire a basal short-axis slice. RV and LV-free-wall (FW) stiffness measurements were compared against each other and also correlated to ventricular mass, RV and LV FW thickness, T1 and T2 relaxation times, and extracellular volume fraction (ECV). Peak transpulmonary pressure gradient and myocardial strain were also acquired on eight dogs by TTE and correlated to RV-FW systolic stiffness. Potential correlations were evaluated by Spearman's rho (rs). RESULTS: RV-FW stiffness was found to be significantly higher than the LV-FW stiffness both during end-systole (ES) (p=0.002) and end-diastole (ED) (p=0.029). Significant correlations were observed between RV-FW ES and LV-FW ED stiffness versus ECV (rs=0.75; p-value=0.05). Non-significant moderate correlations were found between LV-FW ES (rs=0.54) and RV-FW ED (rs=0.61) stiffness versus ECV. Furthermore, non-significant correlations were found between RV or LV-FW stiffness and the remaining variables (rs<0.54; p-value>0.05). CONCLUSION: This study demonstrates the feasibility of determining RV stiffness. The positive correlations between stiffness and ECV might indicate some interdependence between stiffness and myocardial extracellular matrix alterations. However, further studies are warranted to validate our initial observations.

Measuring age-dependent myocardial stiffness across the cardiac cycle using MR elastography: A reproducibility study.

PURPOSE: To assess reproducibility in measuring left ventricular (LV) myocardial stiffness in volunteers throughout the cardiac cycle using MR elastography (MRE) and to determine its correlation with age. METHODS: Cardiac MRE (CMRE) was performed on 29 normal volunteers, with ages ranging from 21 to 73 years. For assessing reproducibility of CMRE-derived stiffness measurements, scans were repeated per volunteer. Wave images were acquired throughout the LV myocardium, and were analyzed to obtain mean stiffness during the cardiac cycle. CMRE-derived stiffness values were correlated to age. RESULTS: Concordance correlation coefficient revealed good interscan agreement with rc of 0.77, with P-value < 0.0001. Significantly higher myocardial stiffness was observed during end-systole (ES) compared with end-diastole (ED) across all subjects. Additionally, increased deviation between ES and ED stiffness was observed with increased age. CONCLUSION: CMRE-derived stiffness is reproducible, with myocardial stiffness changing cyclically across the cardiac cycle. Stiffness is significantly higher during ES compared with ED. With age, ES myocardial stiffness increases more than ED, giving rise to an increased deviation between the two.

Differential patterns of cortical reorganization following constraint-induced movement therapy during early and late period after stroke: A preliminary study.

OBJECTIVE: Constraint-induced movement therapy (CIMT) has been shown to improve upper extremity voluntary movement and change cortical movement representation after stroke. Direct comparison of the differential degree of cortical reorganization according to chronicity in stroke subjects receiving CIMT has not been performed and was the purpose of this study. We hypothesized that a higher degree of cortical reorganization would occur in the early (less than 9 months post-stroke) compared to the late group (more than 12 months post-stroke). METHODS: 17 early and 9 late subjects were enrolled. Each subject was evaluated using transcranial magnetic stimulation (TMS) and the Wolf Motor Function Test (WMFT) and received CIMT for 2 weeks. RESULTS: The early group showed greater improvement in WMFT compared with the late group. TMS motor maps showed persistent enlargement in both groups but the late group trended toward more enlargement. The map shifted posteriorly in the late stroke group. The main limitation was the small number of TMS measures that could be acquired due to high motor thresholds, particularly in the late group. CONCLUSION: CIMT appears to lead to greater improvement in motor function in the early phase after stroke. Greater cortical reorganization in map size and position occurred in the late group in comparison. SIGNIFICANCE: The contrast between larger functional gains in the early group vs larger map changes in the late group may indicate that mechanisms of recovery change over the several months following stroke or that map changes are a time-dependent epiphenomenon.

RF-related heating assessment of extracranial neurosurgical implants at 7T.

PURPOSE: The purpose was to evaluate radiofrequency (RF)-related heating of commonly used extracranial neurosurgical implants in 7-T magnetic resonance imaging (MRI). MATERIALS AND METHODS: Experiments were performed using a 7-T MR system equipped with a transmit/receive RF head coil. Four commonly used titanium neurosurgical implants were studied using a test procedure adapted from the American Society for Testing and Materials Standard F2182-11a. Implants (n=4) were tested with an MRI turbo spin echo pulse sequence designed to achieve maximum RF exposure [specific absorption rate (SAR) level=9.9W/kg], which was further validated by performing calorimetry. Maximum temperature increases near each implant's surface were measured using fiberoptic temperature probes in a gelled-saline-filled phantom that mimicked the conductive properties of soft tissue. Measurement results were compared to literature data for patient safety. RESULTS: The highest achievable phantom averaged SAR was determined by calorimetry to be 2.0±0.1W/kg due to the highly conservative SAR estimation model used by this 7-T MR system. The maximum temperature increase at this SAR level was below 1.0°C for all extracranial neurosurgical implants that underwent testing. CONCLUSION: The findings indicated that RF-related heating under the conditions used in this investigation is not a significant safety concern for patients with the particular extracranial neurosurgical implants evaluated in this study.

Quantification of age-related and per diopter accommodative changes of the lens and ciliary muscle in the emmetropic human eye.

PURPOSE: To calculate age-related and per diopter (D) accommodative changes in crystalline lens and ciliary muscle dimensions in vivo in a single cohort of emmetropic human adults ages 30 to 50 years. METHODS: The right eyes of 26 emmetropic adults were examined using ultrasonography, phakometry, anterior segment optical coherence tomography, and high resolution magnetic resonance imaging. Accommodation was measured both subjectively and objectively. RESULTS: In agreement with previous research, older age was linearly correlated with a thicker lens, steeper anterior lens curvature, shallower anterior chamber, and lower lens equivalent refractive index (all P < 0.01). Age was not related to ciliary muscle ring diameter (CMRD) or lens equatorial diameter (LED). With accommodation, lens thickness increased (+0.064 mm/D, P < 0.001), LED decreased (-0.075 mm/D, P < 0.001), CMRD decreased (-0.105 mm/D, P < 0.001), and the ciliary muscle thickened anteriorly (+0.013 to +0.026 mm/D, P < 0.001) and thinned posteriorly (-0.011 to -0.015, P < 0.01). The changes per diopter of accommodation in LED, CMRD, and ciliary muscle thickness were not related to subject age. CONCLUSIONS: The per diopter ciliary muscle contraction is age independent, even as total accommodative amplitude declines. Quantifying normal biometric dimensions of the accommodative structures and changes with age and accommodative effort will further the development of new IOLs designed to harness ciliary muscle forces.

Retrobulbar vasculature using 7-T magnetic resonance imaging with dedicated eye surface coil.

PURPOSE: To determine the resolution and utility of using a dedicated, single-loop eye coil at 7 T to image the posterior ocular structures and vascular anatomy. METHODS: Imaging was performed on eight subjects (age range 26-54 years, four female, four male) with 7 T using a transmit head coil for excitation and a dedicated 5-cm eye surface receive coil. Acquisition parameters at 7 T for 3D spoiled gradient echo (3D-SPGR) sequences were optimized. RESULTS: It was possible to delineate the retina, sclera, and choroid, and fine details within the anterior and posterior segments of the eye. Retro-orbital and posterior ocular anatomy remained well visualized despite motion and susceptibility artifacts of anterior ocular structures. The ophthalmic arteries and their first-order branches were consistently visualized and improved with registration and summation of repeat scans. Furthermore, the central retinal vessels could be visualized. Intravenous gadolinium contrast reagent did not noticeably improve image quality. CONCLUSIONS: High-resolution 7-T MRI with a dedicated eye coil can provide unique high-resolution noninvasive images of retro-orbital and posterior ocular structural and vascular anatomy and is able to resolve structures as small as the central retina vein.

Magnetic resonance imaging of the initial active stage of equine laminitis at 4.7 T.

Equine laminitis is a severely debilitating disease. There is a poor understanding of the underlying pathophysiology, and traditional imaging modalities have limited diagnostic capacity. High field strength magnetic resonance (MR) imaging allows direct visualization of the laminae, which other modalities do not. This would prove useful both in assessment of clinical patients and in further investigation into the pathophysiology of the disease. The objective of this study was to characterize the anatomic changes within the equine foot associated with the initial active stage of laminitis. Images obtained using a 4.7 T magnet were compared with digital radiographs using histologic diagnosis as the reference standard. Objective measurements and subjective evaluation for both modalities were evaluated for the ability to predict the histologic diagnosis in horses with clinical signs of laminitis as well as in clinically normal horses and horses that were in a population at risk for developing laminitis. Signal intensity and architectural changes within the corium and laminae were readily seen at 4.7 T, and there was a strong association with the histologic diagnosis of active laminitis. Measurements obtained with MR imaging were more sensitive and specific predictors of laminitis than those obtained radiographically. Subjective evaluation with MR imaging was more sensitive than with radiography and should become more specific with greater understanding of normal anatomy.

Constraint-induced movement therapy results in increased motor map area in subjects 3 to 9 months after stroke.

BACKGROUND: Constraint-induced movement therapy (CIMT) has received considerable attention as an intervention to enhance motor recovery and cortical reorganization after stroke. OBJECTIVE: The present study represents the first multi-center effort to measure cortical reorganization induced by CIMT in subjects who are in the subacute stage of recovery. METHODS: A total of 30 stroke subjects in the subacute phase (>3 and <9 months poststroke) were recruited and randomized into experimental (receiving CIMT immediately after baseline evaluation) and control (receiving CIMT after 4 months) groups. Each subject was evaluated using transcranial magnetic stimulation (TMS) at baseline, 2 weeks after baseline, and at 4-month follow-up (ie, after CIMT in the experimental groups and before CIMT in the control groups). The primary clinical outcome measure was the Wolf Motor Function Test. RESULTS: Both experimental and control groups demonstrated improved hand motor function 2 weeks after baseline. The experimental group showed significantly greater improvement in grip force after the intervention and at follow-up (P = .049). After adjusting for the baseline measures, the experimental group had an increase in the TMS motor map area compared with the control group over a 4-month period; this increase was of borderline significance (P = .053). CONCLUSIONS: Among subjects who had a stroke within the previous 3 to 9 months, CIMT produced statistically significant and clinically relevant improvements in arm motor function that persisted for at least 4 months. The corresponding enlargement of TMS motor maps, similar to that found in earlier studies of chronic stroke subjects, appears to play an important role in CIMT-dependent plasticity.

Non-invasive MRI tumor imaging and synergistic anticancer effect of HSP90 inhibitor and glycolysis inhibitor in RIP1-Tag2 transgenic pancreatic tumor model.

PURPOSES: To utilize non-invasive MRI imaging for real-time testing the synergistic effects of HSP90 inhibitor and glycolysis inhibitor for pancreatic cancer therapy in spontaneous pancreatic cancer mouse model. MATERIAL AND METHODS: Transgenic RIP1-Tag2 spontaneous pancreatic cancer mice were treated with geldanamycin (GA, 5 mg/kg) and /or 3-Bromo-pyruvate (3-BrPA, 5 mg/kg) from 8 to 12 weeks of age. Non-invasive MRI imaging measured and calculated the total tumor mass and volumes in real-time and compared to ex vivo tumors size. Serum VEGF levels were measured by ELISA. HSP 90 client protein levels (AKT and VEGF) were measured by western blots. RESULTS: RIP-Tag2 transgenic mice developed pancreatic tumors from 8 to 12 weeks of age. Non-invasive MRI imaging detected primary tumors in pancreas and metastasis in intestine and mesenterium with minimal resolution of 20 mm(3). VEGF, AKT, hexokinase II, and Hsp90 were expressed in the pancreatic cancer tissues from RIP1-Tag2 transgenic mice. Combination of GA and 3-BrPA decreased serum VEGF levels by 70% compared to control group. Non-invasive MRI imaging showed that combination of GA and 3-BrPA inhibited pancreatic tumor and metastasis by more than 90% and significantly prolonged life span of RIP1-Tag2 transgenic pancreatic cancer mice. The synergistic effect of geldanamycin and 3-BrPA is through inhibition of two different pathways on HSP90 for its client protein degradation and on HK II for energy metabolism. CONCLUSION: Non-invasive MRI imaging revealed synergistic effects of Hsp90 inhibitors and glycolysis inhibitors, which may provide a new therapeutic option for pancreatic cancer therapy.

Rodent models for the study of articular fracture healing.

The goal of this study was to document the healing time course and expression of ex vivo cell-based gene delivery in articular fracture models in the mouse and rat. Articular medial intercondylar femoral osteotomy was performed in the stifle (knee) joints of hairless immunocompetent mice and medial or lateral similar osteotomy was performed in athymic nude rats. Genetically modified cells expressing luciferase were delivered in a three-dimensional alginate matrix directly into the osteotomy site. Sensitivity of an in vivo imaging system to detect expression of luciferase was compared between rodents in this fracture model. Osteotomy healing was assessed using high-detail radiography, helical computed tomography (CT), high-field magnetic resonance imaging, and histology. The mouse model was less satisfactory because the small size of the murine femur made reliable assessment of fracture healing restricted to histopathology, and complications occurred in 11/24 mice (45.8%), most frequently transverse supracondylar femoral fracture postoperatively. Gene expression was inconsistently confirmed in mice in vivo for 11 days (p < .003). In rats, high-detail radiography and CT were used to assess osteotomy healing. Magnetic resonance imaging (4.7 T) in rats could produce three-dimensional images that would permit assessment of bone and cartilage, but was time-consuming and expensive. In rats, the only surgical complication, transverse femoral fracture, was reduced from 83.3% with the medial osteotomy to 0% with a lateral osteotomy. In vivo imaging confirmed gene expression in the alginate/cell constructs in rats for at least 4 days (p < .05). The nude rat model has the advantage of larger femora and the ability to implant xenograft cells. A lateral intercondylar osteotomy of the distal femur in the rat can be used to study the healing of articular fractures.