Peter A. Wassenaar

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.

7 Tesla MR imaging of the human eye in vivo

To develop a protocol which optimizes contrast, resolution and scan time for three‐dimensional (3D) imaging of the human eye in vivo using a 7 Tesla (T) scanner and custom radio frequency (RF) coil.

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

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.

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 implants 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.

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.

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 Spearmans 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.

A graphical model of a MOS differential pair in strong and weak inversion

This paper presents a graphical model that shows the relationship between the differential input voltage and the effective gate-source voltages of the input transistors of a MOS differential pair. The model is derived for transistors operating in strong inversion, with a V-I square-law behavior, a power factor n behavior and exponential behavior. The model can be used to analyze more complex circuits.

Quantification of aortic stiffness across the cardiac cycle using magnetic resonance elastography

Background The measurement of arterial stiffness has long been a reliable method of determining the severity and risk involved with many cardiovascular diseases [1]. Magnetic resonance elastography (MRE), a non-invasive MRI-based technique, has recently been applied to measure aortic stiffness [2]. The aim of this study is to determine MRE-derived shear stiffness (μMRE) of the abdominal aorta over the cardiac cycle.

MR elastography-derived right ventricular myocardial stiffness in dogs with congenital pulmonary valve stenosis: correlation with myocardial relaxation times and ECV

Background Cardiac magnetic resonance elastography (CMRE) is a novel imaging technique to noninvasively quantify myocardial stiffness. Previous studies have demonstrated that excess interstitial fluid or fibrosis causes increased myocardial stiffness and also alter T1, T2 relaxation times, and myocardial extracellular volume fraction (ECV). Nonetheless, T1, T2 and ECV have not yet been correlated with either invasive or noninvasive measures of myocardial stiffness. The aim of our study was to demonstrate the feasibility of quantifying right ventricular free wall (RVFW) stiffness using CMRE and correlate it with intrinsic myocardial relaxation times and ECV in dogs with severe congenital pulmonary valve stenosis causing RV hypertrophy.

Abstract B54: Prevention of mouse lung tumors by combinations of budesonide and Targretin or SAHA

Individual chemopreventive drugs have been shown to prevent and slow the growth and progression of mouse lung tumors. Combinations of these chemopreventive agents have been proposed as a strategy for increasing efficacy, while lowering drug toxicity. In addition, non-invasive procedures such as MRI have been suggested as a means to determine the ability of drugs to inhibit the growth of tumors and avoid using serial sacrifices. Three drugs representing different mechanisms of action (budesonide, a nonsteroidal anti-inflammatory; Targretin, a selective activator of RXR; and suberoylanilide hydroxamic acid ( SAHA), a histone deacetylase inhibitor) were used singly and in combination to inhibit development of mouse lung tumors. Lung tumors were induced in female Strain A/J mice by i.p. administration of 100 mg/kg 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol (NNK) once a week for four consecutive weeks. Two weeks after the fourth dose of NNK, the mice started to receive a diet (AIN-76A) containing either1.6 mg/kg budesonide, 160 mg/kg Targretin, 500 mg/kg SAHA, or combinations of budesonide plus either Targretin or SAHA. At Week 21, the multiplicity of lung tumors in control mice (28.13 ± 1.62) was significantly reduced to 10.50 ± 0.74, 15.96 ± 0.90, and 12.42 ± 1.57 by budesonide, Targretin, and SAHA, respectively. The combinations containing budesonide plus Targretin or SAHA demonstrated significantly more inhibition of total tumors than either agent acting alone, resulting in 7.25 ± 0.87 and 5.00 ±1.16 tumors/mouse, respectively. The multiplicity of carcinomas was also significantly reduced by budesonide, Targretin, and SAHA from 5.10 ± 0.83 in control mice to 0.88 ± 0.21, 1.12 ± 0.27, and 0.37 ± 0.15, respectively, whereas the combinations demonstrated a greater efficacy than either agent acting alone, yielding 0.10 ± 0.07, and 0.12 ± 0.12 for the combinations containing Targretin or SAHA, respectively. Mice administered budesonide, Targretin or the control diet were monitored by MRI at Weeks 21, 26 and 31 after the first dose of NNK and groups sacrificed at Weeks 21 and 31 after MRI for tumor counts. The two drugs (budesonide and Targretin) significantly reduced the size and number of tumors when monitored by MRI. At week 21, it was demonstrated by MRI that Targretin and budesonide significantly reduced the multiplicity of total lung tumors by 32% and 64%, respectively, from controls. In conclusion, relative to their individual effects, combinations containing budesonide and either Targretin or SAHA demonstrated greater efficacy in inhibiting both the occurrence of mouse lung tumors and their progression to carcinomas. Supported in part by NCI grant 5R21CA135335. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B54.