Biomedical subjects

M O Leach

Publications and source records attributed to M O Leach.

At least 55 records · Page 3Linked to original sources

PubMed2002

Applications of sliding window reconstruction with cartesian sampling for dynamic contrast enhanced MRI.

Applications of dynamic contrast enhanced MR imaging are increasing and require both high spatial resolution and high temporal resolution. Perfusion studies using susceptibility contrast in particular require very high temporal resolution. The sliding window reconstruction is a technique for increasing temporal resolution. It has previously been applied to radial and spiral sampling, but these schemes require extensive correction and interpolation during image reconstruction. Fourier raw data can be reconstructed simply and quickly using the fast fourier transform (FFT). This paper presents a new Fourier-based sampling scheme and sliding window reconstruction that facilitates fast scanning without needing correction or interpolation. This technique can be used on virtually any MR scanner since it requires no specialized hardware. It is implemented here as a dual gradient echo sequence providing simultaneous T(1)- and T(2)*-weighted images with a time resolution of 1.1 s.

Humans↗

PubMed2002

Comparison between radiological and artificial neural network diagnosis in clinical screening.

The imaging protocol of the UK multicentre magnetic resonance imaging study for screening in women at genetic risk of breast cancer aims to assist in detecting and diagnosing malignant breast lesions. In this paper, we evaluate a three-layer, feed-forward, backpropagation neural network as an artificial radiological classifier using receiver operating characteristic (ROC) curve analysis and compare the results with those obtained using a proposed radiological scoring system for the study which currently supplements the radiologist's clinical opinion, in comparison with histological diagnosis. Based on the 76 symptomatic cases evaluated, descriptive features scored by radiologists showed considerable overlap between benign and malignant, although some features such as irregular contours and heterogeneous enhancement were more often associated with malignant pathology. In this preliminary evaluation, ROC analysis showed that the proposed scoring scheme did not perform well, indicating further refinement is required. When all 23 features were used in the neural network, its performance was poorer than that of the scoring scheme. When only ten features were used, limited to descriptors of enhancement characteristics, the neural network performed similar to the scoring scheme. This comparison shows that the neural network approach to clinical diagnosis has considerable potential and warrants further development.

Breast Neoplasms↗

PubMed2002

Early in vivo detection of metabolic response: a pilot study of 1H MR spectroscopy in extracranial lymphoma and germ cell tumours.

Monitoring therapeutic efficacy is essential in oncological practice. We have investigated the feasibility of using proton (1)H MR spectroscopy (MRS), localized to malignant lymphoma and germ cell lesions outside the cranial cavity, to monitor tumour metabolism in vivo during chemotherapy treatment. (1)H single voxel MRS, (stimulated echo acquisition mode, repetition time/echo time=2000/20 ms) was performed prior to treatment in patients with lymphoma or germ cell tumours, and during the first cycle of chemotherapy. Patient response was assessed by independent clinical follow-up at a median of 57 days (range 44-93 days) post-treatment. All 12 non-cystic lesions scanned showed a signal assigned to choline-containing metabolites (tCho); 9 were scanned both pre- and post-treatment. Changes in the tCho:water ratio following treatment were found to predict subsequent patient response. In seven of these nine patients, the tCho:water ratio decreased in the first post-treatment scan, and all subsequently achieved a partial response to treatment. In the remaining two patients, both of whom progressed on treatment, the tCho:water ratio did not change significantly. Normalized to pre-treatment values, the non-responder group values (1.07 and 0.97) were clearly distinct from the responder group, whose values ranged from 0.43 to below detection level. To our knowledge, this is the first report of (1)H MR spectra from these tumour types and sites. These preliminary results indicate that metabolite signals can be detected using (1)H MRS in these tumour types and locations, as has already been established in the brain, breast and prostate. Moreover, the differential changes observed in the tCho region of the spectrum suggest that (1)H MRS could provide an early and sensitive indicator of metabolic response to chemotherapy.

Adolescent↗

PubMed2002

Assessing response to treatment in breast cancer using magnetic resonance.

Magnetic resonance imaging provides a range of powerful techniques for assessing breast cancer. Contrast enhanced MRI has been shown to provide a sensitive method for assessing primary breast cancer, with increasing emphasis on performing dynamic analysis, and using quantitative analysis techniques. Magnetic resonance spectroscopy provides information on tumour metabolism and has been investigated as a method of assessing response to therapy. The response of metastatic disease from bone cancer has been assessed using T1 weighted methods. MRI provides information on response to treatment early in the course of chemotherapy. Following chemotherapy it provides a sensitive method of assessing residual disease. Both, with conventional treatments and with new antiangiogenic, antivascular and cytostatic treatments, there is a growing role for functional methods of assessing tumour response to treatment.

Bone Neoplasms↗

PubMed2002

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS).

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS) is in progress. The study design, accrual to date, and related research projects are described. Revised accrual rates and expected recruitment are given. 15 cancers have been detected to date, from a total of 1236 screening measurements. This event rate and the tumour grades reported are compared with recent reports from other studies in women at high risk of breast cancer.

Adult↗

PubMed2001

Measuring changes in human tumour vasculature in response to therapy using functional imaging techniques.

Antiangiogenic and antivascular agents provide new approaches to treating tumours. These may avoid many of the problems experienced with current approaches such as inherent and acquired resistance to treatment. Tumours do not grow beyond 1-2 mm(3) in size without the development of new vessels (Folkman, 1971). Such neo-vascularization (angiogenesis) allows tumour cells to increase their nutrient supply, survive and proliferate despite the new vessels often having structural and functional differences compared to normal tissue vasculature. Treatments targeted at tumour vasculature have produced impressive results in animal models (Lindsay et al, 1996; Watson et al, 1996; O'Reilly, 1997; Horsman et al, 1998). These therapies are now entering clinical trials. However, the successful introduction of these therapies into clinical practice will require the development of reliable ways to assess angiogenesis and its modification or inhibition in vivo. Here we discuss some of the emerging imaging techniques that may be useful.

Diagnostic Imaging↗

PubMed2001

Magnetic resonance detects changes in phosphocholine associated with Ras activation and inhibition in NIH 3T3 cells.

Ras is frequently mutated in cancer, and novel therapies are being developed to target Ras signalling. To identify non-invasive surrogate markers of Ras activation and inhibition, we used(31)P magnetic resonance spectroscopy (MRS) and investigated NIH 3T3 cells compared to a mutant ras transfected counterpart. The MR spectra indicated that phosphocholine (PC) levels increased significantly from 3 +/- 2 fmol cell(-1)in NIH 3T3 cells to 13 +/- 4 fmol cell(-1)in the transfected cells. The PC/NTP ratio increased significantly from 0.3 +/- 0.1 to 0.7 +/- 0.3. This could not be explained by either a faster proliferation rate or by alterations in cell cycle distribution. Both cell lines were treated with simvastatin, 17-AAG and R115777, agents which inhibit Ras signalling. Cell proliferation was inhibited in both cell lines. The spectrum of NIH 3T3 cells was not affected by treatment. In contrast, in the ras transfected cells growth inhibition was associated with an average 35 +/- 5% drop in PC levels and a comparable drop in PC/NTP. Thus the MRS visible increase in phosphocholine is associated with Ras activation, and response to treatment is associated with partial reversal of phosphocholine increase in ras transfected cells. MRS might therefore be a useful tool in detecting Ras activation and its inhibition following targeted therapies.

3T3 Cells↗

PubMed2001

In vivo hyperpolarized 129Xe NMR spectroscopy in tumors.

The first in vivo hyperpolarized 129Xe NMR study in experimental tumors is presented. Hyperpolarized 129Xe was dissolved in solutions, and was injected intratumorally in GH-3 prolactinomas in rats and RIF-1 fibrosarcomas in mice. The 129Xe NMR spectra and apparent spin-lattice relaxation times in the two tumor types present characteristic differences. These differences are discussed in terms of xenon exchange between the carrier medium and the tissue compartments.

Animals↗

PubMed2001

Radio-frequency probe for 1H decoupled 31P MRS of the head and neck region.

For optimal performance of 31P MRS at 1.5 Tesla, the use of a double resonant probe is essential to enable the application of 1H decoupling and Nuclear Overhauser Enhancement. This note describes the design, evaluation and safety validation of a versatile and compact probe optimized for 1H decoupled 31P MRS studies of tumors close to the surface of the body, in particular the head and neck region.

Equipment Design↗

PubMed2001

The quantitative 19F-imaging of albumin at 1.5 T: a potential in-vivo tool.

19F-MR-imaging has been used to quantitate albumin concentration in a phantom at 1.5 T. The experimentally derived relationship between albumin concentration and the T1 relaxation time of a fluorinated marker, tetrafluorosuccinic acid (TFSA) was used to calculate the albumin concentration from a quantitative 19F T1 map acquired using a gradient echo sequence. There was close correlation between calculated and actual BSA concentrations (r = 0.99, SE = 0.15). The potentially interfering effect of paramagnetic species on T1 relaxation times was also investigated. Relaxivity data show that albumin concentration measurements should be performed prior to any contrast agent administration.

Albumins↗

PubMed2001

Numerical evaluation of shaped surface coil sensitivity at 63 MHz.

Surface coils are widely used in magnetic resonance studies due to their superior signal to noise (SNR) properties. When shaping planar coils to cylindrical surfaces, the region with maximum sensitivity migrates from the coil plane towards the centre of the shaping radius. The influence of the coil current, the probe and tissue dimensions, the electrical tissue properties and the operating frequency on the B1 field strength of a coil has been studied using statistical methods. This analysis allows the dependence of the axial SNR distribution of circular and square surface coils on shaping radius and coil dimensions to be evaluated quantitatively using 3D finite element methods. An empirically derived equation describing the dependence of the SNR distributions on coil geometry and depth allows the optimum coil dimensions to be predicted for a given shaping radius and desired optimized depth of sensitivity. Simulations are validated experimentally using both B1 and SNR mapping techniques. A comparison between the axial SNR of circular and square coils demonstrated equal SNR distributions of coils with equivalent area at depth.

Magnetic Resonance Imaging↗

PubMed2001

Pre-processed image reconstruction applied to breast and brain MR imaging.

Magnetic resonance imaging (MRI) has emerged as a powerful tool in medical diagnosis and research. Although high spatial resolution images are essential in medical diagnosis and image analysis, high temporal resolution is equally important in applications of dynamic contrast-enhanced MRI or functional brain MRI. In particular, in breast MRI the ability to differentiate between benign and malignant lesions depends, in part, on the temporal resolution of the dynamic image acquisition. New applications of MRI such as multi-feature analysis of image time series data and full 3D functional MRI or event-related functional MRI require high spatial and high temporal resolution for accurate image analysis on a voxel-by-voxel basis. Currently available partial Fourier reconstruction techniques. which effectively improve the time resolution, suffer from a reduced signal to noise ratio in the reconstructed image, a decrease in spatial resolution or reconstruction artefacts, making numerical image analysis difficult. In this work we present an image reconstruction algorithm based on image recovery theory which effectively doubles the temporal resolution and results in an image quality sufficient for further numerical analysis. The developed algorithm requires a full Fourier space acquisition of a pre-contrast or baseline image prior to the reconstruction procedure of the time series partial Fourier data.

Algorithms↗

PubMed2001

Effects of androgen deprivation on prostatic morphology and vascular permeability evaluated with mr imaging.

PURPOSE: To assess magnetic resonance (MR) measures of vascular permeability of prostate cancer treated with androgen deprivation and to correlate these with morphologic appearances and serum prostate-specific antigen (PSA) levels. MATERIALS AND METHODS: MR examinations in 56 consecutive patients with prostate cancer were performed before and after luteinizing hormone-releasing hormone analog treatment. T2-weighted and contrast medium-enhanced T1-weighted MR images were obtained. Pre- and posttreatment comparisons of morphologic features, glandular volume, and enhancement-related parameters (capillary permeability, leakage space, gadolinium accumulation) were made. RESULTS: Fifty-five tumors were seen before treatment; 42, after treatment. Signal intensity in the peripheral zone and seminal vesicles decreased on T2-weighted images in 42 (75%) and 25 (45%) patients, respectively. Median volume in tumor decreased by 65% (95% CI: 55%, 76%); in central gland, by 30% (95% CI: 25%, 35%). Reductions in tumor permeability (P <.001) and changes in washout patterns were observed (P <.001). Tumor permeability reductions coincided with a decrease in serum PSA levels in 91% of patients. A weak correlation between tumor permeability and volume change was seen (r = 0.55, P =.04). Reductions in peripheral zone (P <.001) and central gland (P =.009) permeability were noted. CONCLUSION: Androgen deprivation decreases tumor volume and vascular permeability and impairs detection of prostate cancers. Use of MR estimates of permeability may be an additional way of assessing prostatic tumor response to antiandrogen treatment.

Aged↗

PubMed2001

Application of magnetic resonance imaging to angiogenesis in breast cancer.

Magnetic resonance imaging (MRI) techniques enable vascular function to be mapped with high spatial resolution. Current methods for imaging in breast cancer are described, and a review of recent studies that compared dynamic contrast-enhanced MRI with histopathological indicators of tumour vascular status is provided. These studies show correlation between in vivo dynamic contrast measurements and in vitro histopathology. Dynamic contrast-enhanced MRI is also being applied to assessment of the response of breast tumours to treatment.

Animals↗

PubMed2001

Effects of chronic alcohol consumption on the broad phospholipid signal in human brain: an in vivo 31P MRS study.

BACKGROUND: Phosphorus magnetic resonance spectroscopy (31P MRS) allows for the measurement of phospholipids and their breakdown products in the human brain. Fairly mobile membrane phospholipids give rise to a broad signal that co-resonates with metabolic phosphodiesters. Chronic alcohol exposure increases the rigidity of isolated brain membranes and, thus, may affect the amount and transverse relaxation times (T2) of MRS-detectable phospholipids. We tested the hypothesis that subjects who were heavy drinkers have stiffer membranes than controls who were light drinkers, as reflected in a smaller broad signal component and a shorter T2 of the broad signal in 31P MR spectra of the brain. METHODS: Thirteen alcohol-dependent heavy drinkers (mean age 44 years) were studied by localized 31P MRS in the centrum semiovale and compared with 17 nondependent light drinkers of similar age. The broad component signal was separated from the metabolite signal by convolution difference, which is based on the large difference in line widths of these two signals. Longitudinal and T2 relaxation times were measured using standard methods. RESULTS: The broad component integral was 13% lower in the brain of heavy drinkers compared with light drinkers (p < 0.001) and remained significantly smaller after corrections for both longitudinal and transverse relaxations (p < 0.01). The T2 distribution of the broad component consistently showed two resolvable components in both groups. The fast relaxing component had the same T2 in both groups (T2 = 1.9 msec). The slower relaxing component T2 was 0.6 msec shorter in heavy drinkers compared with light drinkers (p = 0.08). CONCLUSIONS: These results, observed in the absence of white matter volume loss, are consistent with biochemical alterations and higher rigidity of white matter phospholipids associated with long-term chronic alcohol abuse. The observed smaller broad signal component in these relatively young heavy drinkers is a sensitive measure of white matter phospholipid damage.

Adult↗

PubMed2001

Effects of abstinence from alcohol on the broad phospholipid signal in human brain: an in vivo 31P magnetic resonance spectroscopy study.

BACKGROUND: In vivo phosphorus magnetic resonance spectroscopy (31P MRS) at a magnetic field strength of 1.5 T allows measurement of fairly mobile membrane phospholipids in the human brain. We previously showed that subjects who are heavy drinkers had a smaller signal and a shorter transverse relaxation time (T2) of white matter phospholipids than light drinkers, which suggested lower concentrations and molecular mobility of phospholipids in heavy drinkers. The purpose of the present study was to measure if such chronic alcohol-induced white matter tissue changes are persistent in long-term abstinent alcoholics. METHODS: Fourteen abstinent alcoholics (mean age 45 years, seven men and seven women) were studied by localized 31P MRS in the centrum semiovale and were compared with 13 male, alcohol-dependent, heavy drinkers and 23 nondependent light drinkers (17 men, 6 women) of similar age. Methods for measurements of the broad membrane phospholipid signal and its relaxation time were described previously. RESULTS: Phospholipid concentrations and relaxation times in alcoholics abstinent for an average of 31 months were not significantly different from those measured in light drinkers. The contribution of fast and slowly relaxing signal components to the broad phospholipid signal, however, was still different in abstinent alcoholics compared with light drinkers. No effects of sex or of family history of alcoholism were noted on any of our spectroscopic measures within the light-drinking or abstinent groups. CONCLUSIONS: Most of our results suggest at least partial recovery of chronic alcohol-induced white matter phospholipid damage with long-term abstinence. They offer myelination changes and/or dendritic rearborization as a possible mechanism for the commonly observed white matter volume gain with prolonged abstinence. But the results also suggest a persistent abnormality in the nature and/or physical properties of white matter phospholipids in long-term abstinent alcoholics.

Adult↗

PubMed2000

Imaging biochemistry: applications to breast cancer.

The use of magnetic resonance spectroscopy (MRS) to investigate breast tumour biochemistry in vivo is reviewed. To this end, results obtained both from patients in vivo and from tumour extracts and model systems are discussed. An association has been observed between transformation and an increase in phosphomonoesters (PMEs) detected in the 31P MRS spectrum, as well as an increase in choline-containing metabolites detected in the 1H spectrum. A decrease in PME content after treatment is associated with response to treatment as assessed by tumour volume. Experiments in model systems aimed at understanding the underlying biochemical processes are presented, as well as data indicating the usefulness of MRS in monitoring the uptake and metabolism of some chemotherapeutic agents.

Adenocarcinoma↗

PubMed2000

Metabolites of 2'-fluoro-2'-deoxy-D-glucose detected by 19F magnetic resonance spectroscopy in vivo predict response of murine RIF-1 tumors to 5-fluorouracil.

There is a clinical need for early detection of tumor response to therapy. This study aimed to determine whether metabolites of fluorodeoxyglucose (FDG) detected in solid mouse tumors in situ by I9F magnetic resonance spectroscopy (19F MRS) correlated with response to 5-fluorouracil chemotherapy. After injection of FDG (1.4 mmol/kg i.p.), uptake and metabolism was monitored for 2 h in RIF-1 tumors. FDG was detectable immediately, and after 10 min, a second broad peak was detected 5-6 ppm upfield. 19F MRS analysis of cell and tumor extracts in vitro showed that the upfield peak (> or =15% of the total detectable 19F signal) consisted of the epimer alpha-fluorodeoxymannose (FDM) and various conjugates. Mice treated with 5-fluorouracil (130 mg/kg) received, 48 h later, a repeat dose of FDG. The change in the rate of FDM formation, but not the FDG or total 19F signal, correlated significantly with the response to 5-fluorouracil (P = 0.032), suggesting that 19F MRS of FDM metabolism in vivo may be a novel means of predicting tumor response.

Animals↗