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F A Howe

Publications and source records attributed to F A Howe.

54 records · Page 3Linked to original sources

Application of magnetic resonance neurography in the evaluation of patients with peripheral nerve pathology.

Currently, diagnosis and management of disorders involving nerves are generally undertaken without images of the nerves themselves. The authors evaluated whether direct nerve images obtained using the new technique of magnetic resonance (MR) neurography could be used to make clinically important diagnostic distinctions that cannot be readily accomplished using existing methods. The authors obtained T2-weighted fast spin-echo fat-suppressed (chemical shift selection or inversion recovery) and T1-weighted images with planes parallel or transverse to the long axis of nerves using standard or phased-array coils in healthy volunteers and referred patients in 242 sessions. Longitudinal and cross-sectional fascicular images readily distinguished perineural from intraneural masses, thus predicting both resectability and requirement for intraoperative electrophysiological monitoring. Fascicle pattern and longitudinal anatomy firmly identified nerves and thus improved the safety of image-guided procedures. In severe trauma, MR neurography identified nerve discontinuity at the fascicular level preoperatively, thus verifying the need for surgical repair. Direct images readily demonstrated increased diameter in injured nerves and showed the linear extent and time course of image hyperintensity associated with nerve injury. These findings confirm and precisely localize focal nerve compressions, thus avoiding some exploratory surgery and allowing for smaller targeted exposures when surgery is indicated. Direct nerve imaging can demonstrate nerve continuity, distinguish intraneural from perineural masses, and localize nerve compressions prior to surgical exploration. Magnetic resonance neurography can add clinically useful diagnostic information in many situations in which physical examinations, electrodiagnostic tests, and existing image techniques are inconclusive.

Adolescent↗

Noninvasive monitoring of carbogen-induced changes in tumor blood flow and oxygenation by functional magnetic resonance imaging.

PURPOSE: The response of tumors to radiotherapy can be enhanced if carbogen (95% O2, 5% CO2) is breathed. The timing of carbogen administration is critical, and a noninvasive method of monitoring the response of individual tumors would have obvious utility. Functional gradient recalled echo (GRE) magnetic resonance imaging (MRI) techniques are sensitive to changes in the concentrations of deoxyhemoglobin, which, thus, acts as an endogenous contrast agent for oxygenation status and blood flow. METHODS AND MATERIALS: Subcutaneous GH3 prolactinomas in three rats were imaged at 4.7 Tesla with a GRE 1H sequence [echo time (TE) = 20 ms, repetition time (TR) = 80 ms, flip angle = 45 degrees, 1 mm slice, 256 phase encode steps, 4 cm field of view, in-plane resolution 0.08 x 0.08 mm, acquisition time = 4 min]. The rats breathed air or carbogen for four periods of 20 min; three control rats breathed only air. RESULTS: Carbogen breathing caused increases of up to 100% in the GRE image intensity of the tumors. Reversion of air breathing caused the image intensity to fall; essentially the same response was observed with the second cycle of carbogen and air breathing. Control rat tumors showed no significant change. CONCLUSIONS: The response of tumors to carbogen can be monitored noninvasively by GRE MRI. In principle, this could be due to an increase in oxygen content of the blood, a decrease in tumor cell oxygen consumption, or an increase in tumor blood flow. The very large changes in signal intensity suggest that a blood flow increase is the most probable explanation. If this technique can be successfully applied in man, it should be possible to optimize carbogen treatment for individual radiotherapy patients, and perhaps also to enhance tumor uptake of chemotherapeutic agents.

Animals↗

In vivo 31P MRS: absolute concentrations, signal-to-noise and prior knowledge.

Absolute metabolite concentrations have been estimated for nucleoside triphosphate and P(i) from in vivo 31P MR measurements using ISIS localization in a rat tumour model, and the results have been compared to those obtained from acid extracts of the tumours. The aim of the experiment was to assess the performance of four different spectral analysis techniques used for absolute quantitation. The spectral analysis techniques used were two frequency domain methods (peak area integration and Lorentzian fitting--FITSPEC) and two time domain methods (VARPRO and HLSVD). The spectra were acquired in blocks so that the degradation in performance of the four spectral analysis methods with decreasing signal-to-noise ratio (SNR) could be compared and referenced. This and the inclusion of a sophisticated method incorporating prior knowledge yields a more realistic and comprehensive protocol than previously published comparisons. The results suggest that VARPRO is the method of choice for quantitative analysis of tumour 31P MR spectra, giving the most reliable results at low SNR.

Animals↗

Quality assessment in in vivo NMR spectroscopy: V. Multicentre evaluation of prototype test objects and protocols for performance assessment in small bore MRS equipment.

This paper reports the results of multicentre studies aimed at designing, constructing, and evaluating prototype test objects for performance assessment in small-bore MRS systems, by utilizing the test protocols already proposed by the EEC COMAC-BME Concerted Action for clinical MRS equipment. Three classes of test objects were considered: (1) a multicompartment test object for 31P MRS measurements performed with slice-selective sequences; (2) a two-compartment test object for volume-selection 1H MRS; and (3) two-compartment test objects for assessing the performance of experimental systems using ISIS as volume localization sequence in 31P MRS. The results suggested the interest of adopting some of these prototypes for improving the comparison of spectroscopy data obtained from different sites, for providing useful means of quality assurance in experimental MRS, and facilitating the validation of new localization sequences.

Magnetic Resonance Spectroscopy↗

Continuing ischemic damage after acute middle cerebral artery infarction in humans demonstrated by short-echo proton spectroscopy.

BACKGROUND AND PURPOSE: Proton MR spectroscopy is a noninvasive method of monitoring in vivo metabolite concentration changes over time. The aim of this work was to study the ischemic penumbra in humans by measuring the metabolic changes that occur after a middle cerebral artery territory infarction. METHODS: Diagnostic MRI and short-echo time MR spectroscopy were performed on a 1.5-T system. Localized proton MR spectroscopy was performed within the area of cerebral infarction and in a homologous area of the contralateral hemisphere. The residual water resonance in the spectra was removed with the use of the Hankel Lanczos singular value decomposition method, after which peak area estimates were obtained by means of the variable projection time domain fitting analysis. The unsuppressed water signal was used as an internal concentration standard. Ten patients with acute middle cerebral artery infarction were studied within 28 hours of stroke onset and followed up for a period of up to 3 months. RESULTS: Significant changes were seen in the initial spectra from the infarct compared with the contralateral spectra. Lactate, a marker of anaerobic metabolism, was present within the infarct but not detected in the contralateral hemisphere. N-Acetyl aspartate, a neuronal marker, and total creatine were significantly reduced. The initial choline signal, arising from choline-containing compounds within the cell and cell membrane, remained unchanged in the infarct core compared with the contralateral hemisphere. Further reductions in N-acetyl aspartate and total creatine concentrations occurred within the first week. A fall in the lactate concentration was seen within the infarct core during the first 7 to 10 days. Similar reductions in the choline concentration were observed during this period. CONCLUSIONS: The demonstration of the continuing loss of cerebral metabolites within an infarct region suggests that further cell loss occurs up to 10 days after infarction. The continuing loss of neurons may represent continued ischemic damage after middle cerebral artery infarction.

Adult↗

Metabolic consequences of a reversed pH gradient in rat tumors.

We have previously demonstrated (M. Stubbs, Z. M. Bhujwalla, G. M. Tozer, L. M. Rodrigues, R. J. Maxwell, R. Morgan, F. A. Howe, and J. R. Griffiths, NMR Biomed., 5: 351, 1992) that the intracellular pH (pHi) of several rat tumors is higher (> pH 7.0) than that of the tumor extracellular fluid (pHe), in contrast to normal tissues (e.g., liver) in which pHi is lower than pHe. In this paper we confirm a pHe of 6.8 +/- 0.07 (SEM) in Morris hepatoma 9618a by an independent method and report the tissue content of other ions by both 31P magnetic resonance spectroscopy and by conventional analysis in hepatomas and livers in rats. Compared with liver, tissue Na+ was 2-fold higher and tissue K+ was lower. Tissue Ca2+ was 8-fold higher (7.4 +/- 4.3 mumol/g wet weight) and tissue Pi was 2-fold higher (8.5 +/- 1.3 mumol/g wet weight) suggesting the presence of insoluble calcium phosphate. Cl- was unchanged (approximately 40 mumol/g wet weight), whereas HCO3- was lower in the hepatoma (12.4 +/- 0.83 compared to 15.5 +/- 0.76 mumol/g wet weight). Total tissue Mg2+ was similar in both tissues, but free [Mg2+] (calculated by two different methods) was approximately 5-fold lower in the hepatoma. The ATP values were 3.5-fold and [NAD]/[NADH] 9-fold lower in the hepatoma. The results are compatible with the hypothesis that the chronic partial hypoxia of tumor tissue involves changes in the linked equilibria of many ions and metabolites and may help explain such pathologies as calcification.

Adenosine Diphosphate↗

Magnetic resonance neurography of the median nerve.

A magnetic resonance imaging sequence, combining fat and flow suppression with T2 weighting, has been used to produce high conspicuity images of the median nerve within the carpal tunnel. Standard maximum intensity projection techniques were then used to produce three-dimensional (3D) reconstructions of the nerve. Comparison of 3D projections with the wrist in a neutral position and wrist flexed at 45 degrees depicted changes in the shape and course of the median nerve through the carpal tunnel of normal volunteers. In some cases of carpal tunnel syndrome evidence of a localized compression was observed. A 3D image of a nerve may help in the diagnosis of peripheral neuropathy and be an aid to surgery of or near major nerves.

Adult↗

Magnetic resonance neurography.

Radiological methods exist for generating tissue-specific images of bone, vessels, lymphatics, abdominal viscera, and the central nervous system, but there has been no reliable means to generate a clinical image of a nerve. We present the first "image neurogram" and report a method for producing such images by use of commercial magnetic resonance imaging systems. The image depicts a human nerve in situ in relation with a nerve graft, wherein the nerve is rendered in isolation much like a vessel appears in isolation in a subtraction angiogram.

Adult↗

Proton spectroscopy in vivo.

1H magnetic resonance spectroscopy (MRS) has attracted much attention in recent years. Since the proton is the most sensitive stable nucleus for MRS, and since almost all metabolites contain hydrogen atoms, it is possible to perform a noninvasive chemical analysis on tissues deep within the body of a subject. Technical solutions to the elimination of water and lipid signals as well as resolution of the large number of potential metabolite peaks have been found. Most current work is on the brain, much of it in humans. This review begins with a consideration of these technical problems and also localization, editing, quantitation, and interpretation of spectra. Two diseases are considered in detail: cerebral ischemia (including stroke and neonatal ischemic/hypoxic injury) and cancer; a further section briefly reviews studies on other diseases. In the immediate future, 1H MRS is likely to benefit from a number of technical advances: higher field magnets, better control of gradients and eddy currents, more sophisticated radiofrequency (RF) pulses, and 1H-observe/13C-edited spectroscopy all offer potential improvements. Another major improvement will come from increased user-friendliness of clinical spectrometers and use of automated objective methods for spectroscopic data analysis.

Animals↗

Magnetic resonance neurography.

We have made cross-sectional image "neurograms" in which peripheral nerve has a greater signal intensity than that of other tissue. Neurographic images of the rabbit forelimb were obtained using a spin-echo magnetic resonance imaging (MRI) technique that combines fat suppression and diffusion weighting. After fat suppression the nerve shows up in relative isolation and is brighter than the surrounding tissue due to its longer T2 relaxation time of approximately 50 ms compared to approximately 27 ms for muscle. The addition of pulsed gradients for diffusion weighting of the MR signal further enhances the intensity of the nerve signal relative to that of surrounding muscle tissue. The greater diffusional anisotropy of nerve tissue (D parallel/D perpendicular = 3.1) compared to that of muscle (D parallel/D perpendicular = 1.9) allows further enhancement of the nerve by a subtraction of two diffusion-weighted images, one with the gradients oriented parallel and one with the gradients oriented perpendicular to the nerve orientation. We show that by manipulation of the MRI parameters, either echo time or pulsed gradient strength, the nerves can be made to show up as the most intense feature. This verifies the feasibility of generating three-dimensional "neurographic" images, analogous to angiograms, but which demonstrate the peripheral nerve tracts in apparent isolation.

Adipose Tissue↗

A two-compartment phosphate-doped gel phantom for localized spectroscopy.

Acrylamide gel loaded with phosphate has been used in two compartment phantoms designed to assess localized spectroscopy techniques. A chemical shift difference of 2.3 ppm was produced by changing the pH from 6 to 8.9. The 31P relaxation times were modified by doping the gels with paramagnetic ions. For a T1 of approximately 1 sec nickel doping gave a T2 of approximately 110 msec and manganese doping gave a T2 of approximately 8 msec. Gel phantoms are more robust than their liquid equivalent and are not prone to leakage. The construction of small compartments with very thin walls is possible, making this type of phantom suitable for small bore imaging/spectroscopy systems.

Acrylic Resins↗

Discrimination of metabolite from lipid and macromolecule resonances in cerebral infarction in humans using short echo proton spectroscopy.

Short-echo proton spectroscopy allows the noninvasive study of metabolites, lipids, and macromolecules in stroke patients, but spectra are difficult to interpret and quantify because narrow metabolite peaks are added to a broad background of lipid and macromolecule peaks. "Metabolite nulling" was used to distinguish the lactate peak from underlying lipid and macromolecule peaks. Increases in the lipid and macromolecule peaks were initially observed within the region of infarction in all patients, and further increases in lipid peaks were seen in five of the six patients during the following 6 weeks. The initial high lactate concentration decreases during the first 2 weeks after stroke, whereas lipid and macromolecule signals show a persistent elevation during the same period. Differences in the time courses of the observed changes suggest that lipid, macromolecule, and lactate signals arise from more than one source.

Adult↗

An assessment of 31P MRS as a method of measuring pH in rat tumours.

The contribution of extracellular components to the measurement of pHMRS of a variety of rat tumours (nitrosomethyl urea induced mammary tumours, GH3 prolactinomas, Hepatoma 9618a, UA hepatomas and Walker sarcomas) has been assessed. Acid extractable P(i) was between 2.6 and 12.5 mumol/G wet wt depending on tumour type, and of this 53 +/- 4.8% (mean +/- SEM) was MRS-visible. The P(i) content of tumour exudate was 2-3 mM, of interstitial fluid (sampled from a micropore chamber incorporated within a tumour) 1.7 mM, and of blood plasma 1.95 mM. The mean extracellular volumes of the tumours, measured by distribution of 3H2O and [14C]inulin, were 49-55% depending on tumour type and were at least twice that found in normal liver. Calculations suggested that for most tumours with an extracellular volume not exceeding 55%, at least 65% of the P(i)(MRS) signal was derived from intracellular P(i), and thus that pH(MRS) is a measure of pHi. For each tumour type, pHMRS was measured both in 'pulse-acquire' mode at 1.9 T which may include signals from surrounding tissue, and in localized mode at 4.7 T where the signal came uniquely from tumour tissue. The steady state pHMRS was either neutral or on the alkaline side of neutrality (pH range 7.04-7.37). Raised lactate content and decreased buffering capacity (compared to normal tissues) accompanied these neutral to alkaline pH values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An assessment of artefacts in localized and non-localized 31P MRS studies of phosphate metabolites and pH in rat tumours.

UA hepatomas, GH3 prolactinomas and N-methyl-N-nitrosourea-induced mammary tumours, which were subcutaneously grown in rats, have been studied by 31P MRS using non-localized pulse-acquire, image selected in vivo spectroscopy (ISIS) and one-dimensional chemical shift imaging (1-D CSI) techniques. Comparisons have been made with measurements from acid extracts of these tumour types and surrounding tissues (i.e., muscle and skin). Since muscle containing high concentrations of phosphocreatine (PCr) is often found adjacent to the tumour, we have compared the ratio of the PCr to gamma-NTP peaks in the spectra with the same ratio calculated from the acid extract data, and have used deviations between the two sets of data to assess the discrimination of the MRS localization technique to signals from the tissue surrounding the tumour. Extract data showed an average NTP content of 1.25 mumol/g wet wt for all three tumour types. PCr (at 0.42 mumol/g wet wt), was significant only in the GH3 prolactinoma whereas it was negligible in the other tumour types (< 0.1 mumol/g wet wt). There was good agreement between the ISIS PCr/gamma-NTP ratio and the extract data for all tumours. However, the 1-D CSI data showed an unexpectedly large contamination of the tumour spectrum with PCr signals from the skin which was shown by subsequent phantom experiments to be due to the curved geometry of tumour and skin rather than Fourier bleed. In pH measurements by MRS it was found that biological variability was greater than the effects of artefacts (due to either the chemical shift artefact in the ISIS technique or partial volume effects) in the localization technique. An average pH of 7.2 was observed for all tumours. By initially comparing data from different localization schemes with that from chemical extracts potential sources of error have been highlighted and show that phantom studies alone are not sufficient to fully assess the accuracy of localized MRS data.

Animals↗

Pattern recognition of 31P magnetic resonance spectroscopy tumour spectra obtained in vivo.

Pattern recognition has been applied to the analysis of in vivo 31P NMR spectra. Using four different classes of tumour and three types of normal tissue, cluster analysis and artificial neural networks were successful in separating and classifying the majority of samples analysed. Although the phosphomonoester and P(i) regions appeared to be the most important spectral features, data representing the entire 31P spectrum were required for best separation of the tumour and tissue classes.

Animals↗

Issues in flow and oxygenation dependent contrast (FLOOD) imaging of tumours.

The sensitivity of blood oxygenation level dependent (BOLD) contrast techniques to changes to tumour deoxyhaemoglobin concentration is of relevance to many strategies in cancer treatments. In the context of tumour studies, which frequently involve the use of agents to modify blood flow, there are underlying physiological changes different to those of BOLD in the brain. Hence we use the term, flow and oxygenation dependent (FLOOD) contrast, to emphasize this difference and the importance of flow effects. We have measured the R(2)* changes in a prolactinoma tumour model for a variety of vasoactive challenges [carbogen, 100% oxygen and 100% nitrogen as different breathing gases, and administration of tumour blood flow modifiers such as calcitonin gene related peptide (CGRP), hydralazine and nicotinamide]. In addition we have measured other relevant physiological parameters, such as bioenergetic status from (31)P MRS, and blood pH and glucose, that may change during a vasoactive challenge. Here we discuss how they relate to our understanding of FLOOD contrast in tumours. We frequently observe R(2)* changes that match the expected action of the vascular stimulus: R(2)* decreases with agents expected to improve tumour oxygenation and blood flow, and increases with agents designed to increase tumour hypoxia. Unlike most normal tissues, tumours have a chaotic and poorly regulated blood supply, and a mix of glycolytic and oxidative metabolism; thus the response to a vasoactive challenge is not predictable. Changes in blood volume can counteract the effect of blood oxygenation changes, and changes in blood pH and glucose levels can alter oxygen extraction. This can lead to R(2)* changes that are smaller or the reverse of those expected. To properly interpret FLOOD contrast changes these effects must be accounted for.

Animals↗

Relaxation times in paramagnetically doped agarose gels as a function of temperature and ion concentration.

Tissue equivalent gels of NMR phantoms have been investigated at 3.4 MHz. The proton T1 and T2 relaxation times have been measured in Ni++ and Cu++ doped agarose gels as a function of temperature and ion concentration. Ni-agarose gels have the lower T1 temperature dependence, but gels containing both Cu++ and Ni++ can be produced for which T1 has virtually no temperature dependence.

Copper↗

Implementation and evaluation of data compression of MR images.

A full-frame bit-allocation technique of data compression has been implemented using the existing computer facilities of an MR imager. Images reconstructed from compressed data files have been compared with the original image and changes in noise and pixel value measured to evaluate any image degradation introduced by the compression process. A 256 x 256 x 8 bit brain image can be compressed in 20 seconds with a compression ratio of greater than 4:1 without significant loss of information.

Head↗