Thomas W. Redpath

Magnetic resonance imaging screening in women at genetic risk of breast cancer: imaging and analysis protocol for the UK multicentre study

The imaging and analysis protocol of the UK multicentre study of magnetic resonance imaging (MRI) as a method of screening for breast cancer in women at genetic risk is described. The study will compare the sensitivity and specificity of contrast-enhanced MRI with two-view x-ray mammography. Approximately 500 women below the age of 50 at high genetic risk of breast cancer will be recruited per year for three years, with annual MRI and x-ray mammography continuing for up to 5 years. A symptomatic cohort will be measured in the first year to ensure consistent reporting between centres. The MRI examination comprises a high-sensitivity three-dimensional contrast-enhanced assessment, followed by a high-specificity contrast-enhanced study in equivocal cases. Multiparametric analysis will encompass morphological assessment, the kinetics of contrast agent uptake and determination of quantitative pharmacokinetic parameters. Retrospective analysis will identify the most specific indicators of malignancy. Sensitivity and specificity, together with diagnostic performance, diagnostic impact and therapeutic impact will be assessed with reference to pathology, follow-up and changes in diagnostic certainty and therapeutic decisions. Mammography, lesion localisation, pathology and cytology will be performed in accordance with the UK NHS Breast Screening Programme quality assurance standards. Similar standards of quality assurance will be applied for MR measurements and evaluation.

Aortic distensibility and stiffness index measured by magnetic resonance imaging in patients with Marfan's syndrome.

OBJECTIVES--To use magnetic resonance imaging to measure the elastic properties of the aorta of adults with Marfans syndrome and to compare these results with those obtained by echocardiography. PATIENTS AND METHODS--12 patients with Marfans syndrome and 12 controls matched for age. Transverse luminal areas of the ascending and descending aorta were measured using electrocardiographic gated magnetic resonance imaging. Echocardiography was used to measure the diameter of the ascending aorta and aortic arch in patients with Marfans syndrome. Blood pressure was measured during both scans. RESULTS--In diastole, transverse luminal areas of the ascending and descending aorta were significantly greater in patients with Marfans syndrome when measured by magnetic resonance imaging and corrected for body surface area; P < 0.02 and P < 0.05 respectively. Patients with Marfans syndrome had a higher stiffness index (112.77 v 5.78, P < 0.05) and a lower distensibility (0.0066 v 0.0105, P < 0.05) than controls. Results produced by MRI and echocardiography were not significantly different. CONCLUSIONS--Magnetic resonance imaging gives good quality reproducible images of the ascending and descending aorta. In patients with Marfans syndrome, aortic distensibility and stiffness index measured by magnetic resonance imaging were abnormal (but did not always relate directly to the size of the aorta.

Accuracy of T1 measurement in dynamic contrast-enhanced breast MRI using two- and three-dimensional variable flip angle fast low-angle shot

In vivo T1 measurements, used to monitor the uptake of contrast agent by tissues, are typically performed as a first step in implementing compartmental analysis of contrast‐enhanced breast magnetic resonance imaging (MRI) data. We have extended previously described methodology for in vivo T1 measurement (using a variable flip‐angle gradient‐recalled echo technique) to two‐dimensional (2D), fast low‐angle shot (FLASH). This approach requires computational modeling of slice‐selective radiofrequency (RF) excitation to correct for nonrectangular slice profiles. The accuracy with which breast tissue T1 values can be measured by this approach is examined: T1 measurements from phantom and in vivo image data acquired with 2D and 3D FLASH imaging sequences are presented. Significant sources of error due to imaging pulse sequence quality and RF transmit field nonuniformity in the breast coil device that will have detrimental consequences for compartmental analysis are identified. Rigorous quality assurance programs with calibrated phantoms are thus recommended, to verify the accuracy with which T1 measurements are obtained. J. Magn. Reson. Imaging 1999;9:163–171.

A new method of NMR flow imaging

Describes a new and general approach to imaging flowing fluids by nuclear magnetic resonance (NMR). The technique described uses the phase of the signal in order to obtain a measure of the magnitude and direction of the flow. Images of a phantom are presented which demonstrate the implementation of this technique in conjunction with the spin-warp imaging method (Edelstein et al., 1980).

The accuracy of pharmacokinetic parameter measurement in DCE-MRI of the breast at 3 T.

The purpose of this work is to quantify the accuracy of pharmacokinetic parameter measurement in DCE-MRI of breast cancer at 3 T in relation to three sources of error. Individually, T1 measurement error, temporal resolution and transmitted RF field inhomogeneity are considered. Dynamic contrast enhancement curves were simulated using standard acquisition parameters of a DCE-MRI protocol. Errors on pre-contrast T1 due to incorrect RF spoiling were considered. Flip angle errors were measured and introduced into the fitting routine, and temporal resolution was also varied. The error in fitted pharmacokinetic parameters, K(trans) and v(e), was calculated. Flip angles were found to be reduced by up to 55% of the expected value. The resultant errors in our range of K(trans) and v(e) were found to be up to 66% and 74%, respectively. Incorrect T1 estimation results in K(trans) and v(e) errors up to 531% and 233%, respectively. When the temporal resolution is reduced from 10 to 70 s K(trans) drops by up to 48%, while v(e) shows negligible variation. In combination, uncertainties in tissue T1 map and applied flip angle were shown to contribute to errors of up to 88% in K(trans) and 73% in v(e). These results demonstrate the importance of high temporal resolution, accurate T1 measurement and good B1 homogeneity.

The effect of partial removal of the nucleus pulposus from the intervertebral disc on the response of the human annulus fibrosus to compression.

OBJECTIVE To determine how partial removal of the nucleus changes the response of the annulus to compression. DESIGN The deformation of the annulus in the mid-sagittal plane, during compression, was determined from digital video images. BACKGROUND Several studies have shown that removal of the nucleus changes the external behaviour of the intervertebral disc, but few studies have investigated changes to internal behaviour. METHODS Six frozen human lumbar discs were bisected in the sagittal plane to produce 12 specimens. The cut surfaces were marked with seven dots of Alcian blue stain. The specimens were sealed, enabling their internal structure to be viewed directly by a digital video recording system, and thawed. The video system recorded the response of each specimen as it was compressed by up to 1.8 mm at a rate of 0.2 mm s(-1). The displacements of the Alcian blue marks were measured using an image analysis program. Magnetic resonance imaging was used to investigate the validity of this technique. RESULTS Partial removal of the nucleus changed the way that the disc deformed under compression. A highly significant change in direction of movement was seen in the inner posterior region of the annulus. CONCLUSIONS Partial removal of the nucleus changes the response of the annulus to compression. RELEVANCE Partial denucleation of the human intervertebral disc is shown to change the direction of bulging of the inner annulus when the disc is compressed. Increases in shear stress, arising from these changes, may lead to further disc degeneration in the form of circumferential tears.

In vivo proton magnetic resonance spectroscopy of breast cancer: a review of the literature

An emerging clinical modality called proton magnetic resonance spectroscopy (1H-MRS) enables the non-invasive in vivo assessment of tissue metabolism and is demonstrating applications in improving the specificity of MR breast lesion diagnosis and monitoring tumour responsiveness to neoadjuvant chemotherapies. Variations in the concentration of choline-based cellular metabolites, detectable with 1H-MRS, have shown an association with malignant transformation of tissue in in vivo and in vitro studies. 1H-MRS exists as an adjunct to the current routine clinical breast MR examination. This review serves as an introduction to the field of breast 1H-MRS, discusses modern high-field strength and quantitative approaches and technical considerations, and reviews the literature with respect to the application of 1H-MRS for breast cancer.

Serum Concentrations of Myostatin and Myostatin-Interacting Proteins Do Not Differ Between Young and Sarcopenic Elderly Men

Sarcopenia is the loss of muscle size and function during ageing. The aim of this study was to test whether serum concentrations of myostatin and interacting proteins (GASP-1, FLRG, and follistatin) differed between young and elderly sarcopenic men. Isometric knee extensor maximal voluntary contraction and quadriceps cross-sectional area (magnetic resonance imaging measurement) were significantly higher in young (22 ± 2 years; 266 ± 54 N/m; 8,686 ± 1,154 mm(2)) than in mildly sarcopenic (69 ± 3 years; 183 ± 17 N/m; 6,621±718 mm(2)) and severely sarcopenic men (76 ± 6 years; 127 ± 23 N/m; 5,846 ± 591 mm(2)), respectively (p ≤ .01 for all comparisons). There was a trend (p = .06) toward higher FLRG in young (20 ± 8 ng/mL) than in mildly (15 ± 6 ng/mL) and severely sarcopenic men (17 ± 8 ng/mL). Myostatin, follistatin, GASP-1, tumor necrosis factor α, and interleukin-6 did not differ significantly. Insulin-like growth factor-1 and free testosterone were both significantly lower in sarcopenic men (p < .001). This suggests that altered serum concentrations of myostatin and myostatin-interacting proteins are not contributing to sarcopenia with the possible exception of FLRG.

The relationship between vascular and metabolic characteristics of primary breast tumours

The objective of this study was to investigate the relationship between vascular and metabolic characteristics of breast tumours in vivo, using contrast-enhanced dynamic MRI and 2-[18F] fluoro-2-deoxy-d-glucose (FDG) PET imaging. Twenty patients with large or locally advanced primary breast cancers were imaged prior to therapy. MRI data were acquired using a dynamic gradient echo sequence and analysed using two pharmacokinetic models. Static PET data were acquired in 2D mode. A significant association (P<0.05) was observed between the calculated exchange rate constants of both pharmacokinetic models and calculated PET FDG dose uptake ratios (DUR). Statistical analysis showed that the exchange rate constants can explain between 27 and 44% of the variance observed in the PET FDG uptake ratios. A relationship was demonstrated between the vascular and metabolic characteristics of primary breast tumours showing that any assessment of tumour metabolic activity using PET may be controlled at least in part by delivery of uptake agent due to the vascular characteristics of the tumour. MRI and PET provide methods of assessing breast tumour vascularity and metabolism in vivo using the exchange rate constants of dynamic MRI, and DUR of PET, respectively, these measures being related but not equivalent.

B1 transmission-field inhomogeneity and enhancement ratio errors in dynamic contrast-enhanced MRI (DCE-MRI) of the breast at 3T.

To quantify B1 transmission‐field inhomogeneity in breast imaging of normal volunteers at 3T using 3D T1‐weighted spoiled gradient echo and to assess the resulting errors in enhancement ratio (ER) measured in dynamic contrast‐enhanced MRI (DCE‐MRI) studies of the breast.