Biomedical subjects

Mark A Horsfield

Publications and source records attributed to Mark A Horsfield.

8 recordsLinked to original sources

PubMed2004

Algorithms for calculation of kinetic parameters from T1-weighted dynamic contrast-enhanced magnetic resonance imaging.

PURPOSE: To quantify the errors involved in calculating dynamic parameters (K(trans) and ve) from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scans, and to develop alternative analyses to improve accuracy or increase processing speed. MATERIALS AND METHODS: This paper presents three different ways of handling the discrete samples of the arterial input and tissue response data with increasing fidelity, with which this continuous arterial input function (AIF) is represented. Also, a new noniterative approach to parameter estimation was developed from one used previously for analysis of radioactive tracer concentrations in radioangiography. The analysis methods were tested using simulated data. RESULTS: The more sophisticated schemes for data processing give more accurate parameter estimates when data are sparsely sampled, at least for the AIF that we modeled. The noniterative algorithm is very rapid in execution, but was more susceptible to measurement errors. CONCLUSION: The improved algorithms presented should be useful when the AIF and tissue response are sparsely sampled. The noniterative approach may be suitable for semiquantitative visualization, or where the AIF and tissue response are sampled accurately and with a small time interval between samples.

Algorithms↗

PubMed2004

The role of imaging in the clinical development of antiangiogenic agents.

Early clinical development of novel antiangiogenesis agents is hampered by the fact that classic response end points are unlikely to be relevant and there is a lack of validated surrogate markers of efficacy. Toxicity-based decisions for dose setting and tumor size measurements by standard imaging probably are not be applicable. Because these agents modify a multitude of biologic processes that may cause early measurable effects, there is great interest in developing imaging tests that are sensitive to changes in tissue function. This article discusses the development of such "functional" clinical imaging and attempts to address the questions that are being asked of imaging departments by oncologists and pharmaceutical companies.

Angiogenesis Inhibitors↗

PubMed2004

Dynamic change of the upper airway during inhalation via aerosol delivery devices.

Although it is likely that the upper airway is a major factor in the large inter- and intra-subject variation in deposition of inhaled drug aerosols in the lung, data on the configuration of the upper airway during inhalation is sparse. We have developed a unique method, using magnetic resonance imaging, to reconstruct the upper airway in three dimensions during inhalation from aerosol devices used to deliver medication to patients with asthma, chronic obstructive pulmonary disease, and cystic fibrosis. Ten healthy adults were imaged while inhaling from a pressurized metered dose inhaler (pMDI), a spacer used with pMDI (spacer), and a high-resistance dry powder inhaler, the Turbuhaler (DPI). The mean cross-sectional area of the oropharyngeal region was significantly larger (Wilcoxon's signed-rank test with Bonferroni correction, p < 0.0167) when the DPI (281 [143] mm2, mean [SD]) was used compared to the spacer (205 [32] mm2, p = 0.016) or pMDI (152 [48] mm2, p = 0.013). Considerable variations in the cross-sectional areas of the oral cavity, oropharynx, and larynx were seen when compared to the upper trachea. The main cause for this was the varying position of the tongue during inhalation via the devices. Although differences were observed when comparing the total volume of the upper airway during inhalation via the DPI (70 [17] cm3) to the pMDI (56 [20] cm3, p = 0.037) or spacer (59 [12] cm3, p = 0.022), these did not reach significance. This study shows that there are very significant variations in the configuration of the upper airway when different devices are used for inhalation. These changes are likely to be produced by a number of factors, including tongue position, device airflow resistance, and patient effort.

Administration, Inhalation↗

PubMed2003

Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: results from two phase I studies.

PURPOSE: PTK787/ZK 222584 (PTK/ZK), an orally active inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, inhibits VEGF-mediated angiogenesis. The pharmacodynamic effects of PTK/ZK were evaluated by assessing changes in contrast-enhancement parameters of metastatic liver lesions using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced colorectal cancer treated in two ongoing, dose-escalating phase I studies. PATIENTS AND METHODS: Twenty-six patients had DCE-MRI performed at baseline, day 2, and at the end of each 28-day cycle. Doses of oral PTK/ZK ranged from 50 to 2000 mg once daily. Tumor permeability and vascularity were assessed by calculating the bidirectional transfer constant (Ki). The percentage of baseline Ki (% of baseline Ki) at each time point was compared with pharmacokinetic and clinical end points. RESULTS: A significant negative correlation exists between the % of baseline Ki and increase in PTK/ZK oral dose and plasma levels (P =.01 for oral dose; P =.0001 for area under the plasma concentration curve at day 2). Patients with a best response of stable disease had a significantly greater reduction in Ki at both day 2 and at the end of cycle 1 compared with progressors (mean difference in % of baseline Ki, 47%, P =.004%; and 51%, P =.006; respectively). The difference in % of baseline Ki remained statistically significant after adjusting for baseline WHO performance status. CONCLUSION: These findings should help to define a biologically active dose of PTK/ZK. These results suggest that DCE-MRI may be a useful biomarker for defining the pharmacological response and dose of angiogenesis inhibitors, such as PTK/ZK, for further clinical development.

Administration, Oral↗

PubMed2003

Guidelines for using quantitative magnetization transfer magnetic resonance imaging for monitoring treatment of multiple sclerosis.

Quantitative evaluation of brain magnetic resonance imaging (MRI) scans is now an accepted part of the trial of new putative treatments for multiple sclerosis (MS). However, conventional MRI is not pathologically specific, and it does not reveal the details of the pathological processes that underlie the progression of the disease. Magnetization transfer (MT) imaging is a relatively new quantitative technique that appears to offer some pathological specificity, and can be used to monitor the changes over time in both individual lesions and the central nervous system as a whole. This paper considers the case for incorporating MT imaging into new clinical trials, so that the utility of MT for monitoring the modification of MS progression by treatment can be assessed. Specific guidelines for implementing MT imaging as part of a large multicenter clinical trial are given, and practical considerations when planning such a trial are detailed. It is anticipated that MT imaging will be incorporated into many new trials in the near future.

Brain↗

PubMed2002

Spatial normalization and averaging of diffusion tensor MRI data sets.

Diffusion tensor magnetic resonance imaging (DT-MRI) is unique in providing information about both the structural integrity and the orientation of white matter fibers in vivo and, through "tractography", revealing the trajectories of white matter tracts. DT-MRI is therefore a promising technique for detecting differences in white matter architecture between different subject populations. However, while studies involving analyses of group averages of scalar quantities derived from DT-MRI data have been performed, as yet there have been no similar studies involving the whole tensor. Here we present the first step towards realizing such a study, i.e., the spatial normalization of whole tensor data sets. The approach is illustrated by spatial normalization of 10 DT-MRI data sets to a standard anatomical template. Both qualitative and quantitative approaches are described for assessing the results of spatial normalization. Techniques are then described for combining the spatially normalized data sets according to three definitions of average, i.e., the mean, median, and mode of a distribution of tensors. The current absence of, and hence need for, appropriate statistical tests for comparison of results derived from group-averaged DT-MRI data sets is then discussed. Finally, the feasibility of performing tractography on the group-averaged DT-MRI data set is investigated and the possibility and implications of generating a generic map of brain connectivity from a group of subjects is considered.

Adult↗

PubMedDate not supplied

Applications of diffusion-weighted and diffusion tensor MRI to white matter diseases - a review.

This paper reviews the current applications of diffusion-weighted and diffusion tensor MRI in diseases of the brain white matter. The contribution that diffusion-weighted imaging has made to our understanding of white matter diseases is critically appraised. The quantitative nature of diffusion MRI is one of its major attractions; however, this is offset by the more advanced hardware required to collect diffusion-weighted images reliably, and the more complex processing to produce quantitative parametric diffusion images. With the now common availability of scanners equipped to perform echo-planar imaging, the acquisition of diffusion tensor images is sure to become more widespread and routine.

Alzheimer Disease↗

PubMedDate not supplied

Sensitivity-encoded diffusion tensor MR imaging of the cervical cord.

The aim of this study was to apply sensitivity-encoding (SENSE) echo-planar imaging (EPI) to diffusion tensor MR imaging of the cervical cord, an anatomic region where MR imaging is particularly challenging. This technique was implemented with a SENSE reduction factor of 2 and used for imaging a water phantom and five healthy volunteers. Off-resonance artifacts were notably reduced compared with those of full-FOV EPI sequences. This approach to diffusion tensor MR imaging of the cervical cord is promising for future, more extensive clinical applications.

Adult↗