Biomedical subjects

M F Lythgoe

Publications and source records attributed to M F Lythgoe.

At least 19 recordsLinked to original sources

PubMed2001

Simultaneous noninvasive measurement of CBF and CBV using double-echo FAIR (DEFAIR).

A new method for measuring cerebral blood flow (CBF) and cerebral blood volume (CBV) noninvasively using MRI is presented. The approach is based on the technique of arterial spin labelling (ASL), in which CBF-based contrast is generated by controlled modulation of the longitudinal magnetization of the blood. The proposed method also uses differences in T(2) between tissue and blood to differentiate the two compartments and allow assessment of the relative size of each. Two successive EPI images are acquired following spin preparation using either a slice-selective or global inversion pulse, and the technique is therefore referred to as double-echo FAIR (DEFAIR). DEFAIR is demonstrated in the normal gerbil brain and during hypothermia, where reductions of both CBF and CBV are known to occur. It is also shown theoretically that this method can be extended to include a measurement of oxygen extraction fraction. The main drawbacks of the technique are the long acquisition time and relatively low sensitivity to hemodynamic changes compared to conventional qualitative T2(*)-weighted BOLD contrast, which may limit its applicability and practical use in monitoring functional cerebral activation. However, the technique can be used repetitively in longer-term time course studies due to its noninvasive and quantitative nature.

Animals↗

PubMed2001

Cerebrovascular reactivity following focal brain ischemia in the rat: a functional magnetic resonance imaging study.

An essential goal of stroke research is to identify potentially salvageable regions of brain that may respond to therapy. However, current imaging methods are inadequate for this purpose. We therefore used dynamic magnetic resonance imaging of vascular reactivity following focal occlusion in the rat to determine whether measurement of perfusion reserve would help resolve this problem. We used the increase in blood-oxygen-level-dependent (BOLD) signal that occurs in normal brain following a CO2 challenge, to map vascular reactivity over the brain at 30-min intervals for 3.5 h after complete (CO) or partial (PO) focal ischemia. We assessed the regional correspondence between reactivity changes and areas of lowered apparent diffusion coefficient (ADC) and initial perfusion deficit. The area of lowered ADC was significantly smaller in the PO group compared to the CO group despite similar areas of perfusion deficit (P < 0.05). We identified four distinct areas within hypoperfused brain: a core area with low/absent reactivity and low ADC; borderzone areas with normal reactivity and either reduced ADC (CO group) or normal ADC (PO group); and an area with normal ADC and reduced/absent reactivity. In all ischemic regions, the BOLD peak arrival time in the brain was delayed or absent. There was a negative correlation between BOLD peak latency time and ADC (r = -0.42, P < 0.001), although latency alone did not differentiate individual ischemic regions. In conclusion, combining perfusion, ADC, and vascular reactivity mapping of the ischemic brain enables improved discrimination of core and borderzone regions.

Animals↗

PubMed2001

High resolution MRI reveals global changes in brains of Cln3 mutant mice.

Batten disease, the juvenile-onset form of neuronal ceroid lipofuscinosis (NCL), is a progressive neurodegenerative disorder of childhood with an age of onset of 5-10 years of age. JNCL is caused by mutations in the CLN3 gene which encodes a membrane protein of unknown function. Magnetic resonance imaging of the brain of juvenile NCL patients has revealed changes in signal intensity and tissue atrophy, predominantly in the cortex and cerebellum. A mouse model for Batten disease was created by targeted disruption of the murine Cln3 gene in order to further understanding of the pathophysiology of Batten disease and to evaluate potential therapeutic approaches. Several features of the disease are displayed by Cln3 mice including accumulation of characteristic storage material in neurons. The aim of this work was to investigate neurodegeneration in the Cln3 mouse model using high resolution magnetic resonance imaging to measure signal intensity ratios in selected regions of interest. Global changes were observed in the brains of 12-month-old mutant mice that mirror those seen in juvenile NCL patients. There is a decrease in signal intensity ratio in grey matter regions including cortex, hippocampus and cerebellum, tissues where neuronal storage accumulation and cell loss have been seen in the mouse model. The alterations seen in Cln3 mutant mice support the validity of further imaging studies and suggest that this method will have application in assessment of therapeutic approaches in the study of mutant mouse models of NCL including the Cln3 mouse.

Animals↗

PubMed2000

Acute changes in MRI diffusion, perfusion, T(1), and T(2) in a rat model of oligemia produced by partial occlusion of the middle cerebral artery.

Oligemic regions, in which the cerebral blood flow is reduced without impaired energy metabolism, have the potential to evolve toward infarction and remain a target for therapy. The aim of this study was to investigate this oligemic region using various MRI parameters in a rat model of focal oligemia. This model has been designed specifically for remote-controlled occlusion from outside an MRI scanner. Wistar rats underwent remote partial MCAO using an undersize 0.2 mm nylon monofilament with a bullet-shaped tip. Cerebral blood flow (CBF(ASL)), using an arterial spin labeling technique, the apparent diffusion coefficient of water (ADC), and the relaxation times T(1) and T(2) were acquired using an 8.5 T vertical magnet. Following occlusion there was a decrease in CBF(ASL) to 35 +/- 5% of baseline throughout the middle cerebral artery territory. During the entire period of the study there were no observed changes in the ADC. On occlusion, T(2) rapidly decreased in both cortex and basal ganglia and then normalized to the preocclusion values. T(1) values rapidly increased (within approximately 7 min) on occlusion. In conclusion, this study demonstrates the feasibility of partially occluding the middle cerebral artery to produce a large area of oligemia within the MRI scanner. In this region of oligemic flow we detect a rapid increase in T(1) and decrease in T(2). These changes occur before the onset of vasogenic edema. We attribute the acute change in T(2) to increased amounts of deoxyhemoglobin; the mechanisms underlying the change in T(1) require further investigation.

Animals↗

PubMed2000

Burst excitation for quantitative diffusion imaging with multiple b-values.

A quantitative imaging sequence has been developed to exploit the intrinsic sensitivity of Burst NMR data to molecular diffusion. In the scan time of a single spin echo experiment, it is possible to acquire many images of the same slice, with a different T(2) and diffusion weighting. Under favorable conditions, it is possible to obtain both the diffusion coefficient and T(2) from the same experiment; or, by correcting for T(2) relaxation using a control image, more precise diffusion coefficients may be measured. The quantitative values in rat brain are in agreement with those from conventional experiments. The major gains of this method are the potentially reduced scan time, the higher number of acquired images corresponding to different diffusion weightings, the reduced sensitivity to inter-scan motion artifact and to local variations in magnetic susceptibility, and an automatic co-registration between T(2) and diffusion images. Problems with the sequence include a lower signal-to-noise ratio than is achievable with diffusion-weighted spin-echo imaging, the limitation of measuring only in-plane components of diffusion and, at present, single-slice acquisition.

Animals↗

PubMed2000

The measurement of diffusion and perfusion in biological systems using magnetic resonance imaging.

The aim of this review is to describe two recent developments in the use of magnetic resonance imaging (MRI) in the study of biological systems: diffusion and perfusion MRI. Diffusion MRI measures the molecular mobility of water in tissue, while perfusion MRI measures the rate at which blood is delivered to tissue. Therefore, both these techniques measure quantities which have direct physiological relevance. It is shown that diffusion in biological systems is a complex phenomenon, influenced directly by tissue microstructure, and that its measurement can provide a large amount of information about the organization of this structure in normal and diseased tissue. Perfusion reflects the delivery of essential nutrients to tissue, and so is directly related to its status. The concepts behind the techniques are explained, and the theoretical models that are used to convert MRI data to quantitative physical parameters are outlined. Examples of current applications of diffusion and perfusion MRI are given. In particular, the use of the techniques to study the pathophysiology of cerebral ischaemia/stroke is described. It is hoped that the biophysical insights provided by this approach will help to define the mechanisms of cell damage and allow evaluation of therapies aimed at reducing this damage.

Animals↗

PubMed1999

Early changes in water diffusion, perfusion, T1, and T2 during focal cerebral ischemia in the rat studied at 8.5 T.

The time evolution of water diffusion, perfusion, T1, and T2 is investigated at high magnetic field (8.5 T) following permanent middle cerebral artery occlusion in the rat. Cerebral blood flow maps were obtained using arterial spin tagging. Although the quantitative perfusion measurements in ischemic tissue still pose difficulties, the combined perfusion and diffusion data nevertheless distinguish between a "moderately affected area," with reduced perfusion but normal diffusion; and a "severely affected area," in which both perfusion and diffusion are significantly reduced. Two novel magnetic resonance imaging observations are reported, namely, a decrease in T2 and an increase in T1, both within the first few minutes of ischemia. The rapid initial decrease in T2 is believed to be associated with an increase in deoxyhemoglobin levels, while the initial increase in T1 may be related to several factors, such as flow effects, an alteration in tissue oxygenation, and changes in water environment.

Animals↗

PubMed1999

The relationship between magnetic resonance diffusion imaging and autoradiographic markers of cerebral blood flow and hypoxia in an animal stroke model.

This study examined the relationship between magnetic resonance diffusion imaging and autoradiographic markers of cerebral blood flow (99mTc-hexamethylpropylene amine oxime) and cerebral hypoxia (125I-iodoazomycin arabinoside) in a rat model of stroke. Middle cerebral artery occlusion in the rat was performed using an intraluminal suture approach. Diffusion, hypoxia, and blood flow maps were acquired 2 hr following occlusion, and were compared with T2 images and histology at 7 hr. Two hours following middle cerebral artery occlusion the lesion distributions from the diffusion maps and hypoxic autoradiographs were similar. The blood flow threshold for increased uptake of the hypoxic marker was approximately 34 +/- 7% of the normal flow. The combination of diffusion or hypoxic images with perfusion maps allowed differentiation between four regions: 1) normal tissue; 2) a region of decreased perfusion but normal diffusion and normal uptake of hypoxic marker; 3) a region of decreased perfusion, decreased diffusion and increased uptake of hypoxic marker; 4) a region of decreased perfusion, decreased diffusion and low uptake of hypoxic marker. The areas for increased uptake of hypoxic marker and decreased diffusion are equivalent, indicating similar blood flow thresholds. Regions of oligaemic misery perfusion, ischaemic misery perfusion and lesion core may be delineated with the combination of diffusion or hypoxic images and perfusion maps.

Animals↗

PubMed1999

Implementation of quantitative FAIR perfusion imaging with a short repetition time in time-course studies.

Flow-sensitive alternating inversion recovery (FAIR) is a pulsed arterial spin labeling magnetic resonance imaging method for perfusion quantification. In its standard implementation for quantification with full longitudinal relaxation between acquisitions, its use in time-course investigations of rapidly changing flow values is limited. The time efficiency can be improved by decreasing the repetition time but quantification becomes problematic. This situation is further complicated if a whole-body radiofrequency transmit coil is not used since fresh blood spins will flow in from outside the coil. To alleviate these problems, the use of global pre-saturation is proposed. The resulting expression for the flow signal depends on the relationship between the imaging parameters and the coil inflow time and can be significantly simplified under certain combinations of these parameters. With this implementation of FAIR, quantitative flow maps of gerbil brains were obtained with a 3 minute time resolution in a study of the effects of reperfusion. The pre-occlusion flow measurements were in good agreement with values obtained by the standard FAIR implementation and by other techniques, but the low values following occlusion were underestimated due to the increased transit times.

Animals↗

PubMed1999

Assessment of various parameters in the estimation of differential renal function using technetium-99m mercaptoacetyltriglycine.

Differential renal function (DRF) is an important parameter that should be assessed from virtually every dynamic renogram. With the introduction of technetium-99m mercaptoacetyltriglycine (99mTc-MAG3), a tracer with a high renal extraction, the estimation of DRF might hopefully become accurate and reproducible both between observers in the same institution and also between institutions. The aim of this study was to assess the effect of different parameters on the estimation of DRF. To this end we investigated two groups of children: group A, comprising 35 children with a single kidney (27 of whom had poor renal function), and group B, comprising 20 children with two kidneys and normal global function who also had an associated 99mTc-dimercaptosuccinic acid scan (99mTc-DMSA). The variables assessed for their effect on the estimation of DRF were: different operators, the choice of renal regions of interest (ROIs), the applied background subtraction, and six different techniques for analysis of the renogram. The six techniques were based on: linear regression of the slopes in the Rutland-Patlak plot, matrix deconvolution, differential method, integral method, linear regression of the slope of the renograms, and the area under the curve of the renogram. The estimation of DRF was less dependent upon both observer and method in patients with two normally functioning kidneys than in patients with a single kidney. The inter-observer comparison among children in either group was not dependent on either ROI or background subtraction. However, in patients with poor renal function the method of choice for the estimation of DRF was dependent on background subtraction, though not ROI. In children with two kidneys and normal renal function, the estimation of DRF from the 24 techniques gave similar results. Methods that produced DRF values closest to expected results, from either group of children, were the Rutland-Patlak plot and matrix deconvolution methods.

Area Under Curve↗

PubMed1999

Reperfusion in a gerbil model of forebrain ischemia using serial magnetic resonance FAIR perfusion imaging.

BACKGROUND AND PURPOSE: Existing methods for the quantitative measurement of the changing cerebral blood flow (CBF) during reperfusion suffer from poor spatial or temporal resolution. The aim of this study was to implement a recently developed MRI technique for quantitative perfusion imaging in a gerbil model of reperfusion. Flow-sensitive alternating inversion recovery (FAIR) is a noninvasive procedure that uses blood water as an endogenous tracer. METHODS: Bilateral forebrain ischemia of 4 minutes' duration was induced in gerbils (n=8). A modified version of FAIR with improved time efficiency was used to provide CBF maps with a time resolution of 2.8 minutes after recirculation had been initiated. Quantitative diffusion imaging was also performed at intervals during the reperfusion period. RESULTS: On initiating recirculation after the transient period of ischemia, the FAIR measurements demonstrated either a symmetrical, bilateral pattern of flow impairment (n=4) or an immediate side-to-side difference that became apparent with respect to the cerebral hemispheres in the imaged slice (n=4). The flow in each hemisphere displayed a pattern of recovery close to the preocclusion level or, alternatively, returned to a lower level before displaying a delayed hypoperfusion and a subsequent slow recovery. The diffusion measurements during this latter response suggested the development of cell swelling during the reperfusion phase in the striatum. CONCLUSIONS: The CBF during the reperfusion period was monitored with a high time resolution, noninvasive method. This study demonstrates the utility of MRI techniques in following blood flow changes and their pathophysiological consequences.

Animals↗

PubMed1998

A quantitative method for fast diffusion imaging using magnetization-prepared TurboFLASH.

For the in vivo measurement of the apparent diffusion coefficient (ADC), it is desirable for the total imaging time to be as short as possible. One technique is based on a TurboFLASH acquisition in which the diffusion gradients are inserted into a driven equilibrium Fourier transform (DEFT) combination of hard pulses. However, this sequence has the disadvantage that eddy current-induced inhomogeneities lead to incomplete refocusing of the magnetization during the diffusion preparation and to incorrect ADC values. A modification to the sequence is suggested that eliminates this error by phase-cycling the second 90 degrees pulse of the preparation. This study also investigates the effect of a reduced delay time between acquisitions on the accuracy of the measurement. The quality of the TurboFLASH sequence is demonstrated by experimental validation on an agar phantom and in vivo on the rat brain using a high-field (8.5 T) system. Reduction of the interexperiment delay time is shown to be achievable to a certain degree without compromising the measurement accuracy.

Animals↗

PubMed1998

Estimation and relevance of depth correction in paediatric renal studies.

Measurement of absolute renal function by gamma camera techniques requires knowledge of kidney depth to correct for soft tissue attenuation, there is debate about the need to take depth into account when only relative renal function is estimated. The aim of this study was to derive a formula for renal depth in children and to assess the importance of depth correction when relative renal function is assessed with dimercaptosuccinic acid (DMSA) on the gamma camera. In this study, kidney depths were derived from measurements on abdominal computerised tomography (CT) images in 57 children in the supine position with two normally located kidneys. Using best-subset regression analysis, one formula for both left and right kidney depth (KD, cm) was developed based on the easily measured parameters of height (H, cm) and body weight (W, kg). The inclusion of extra variables was found to significantly improve the model compared with a model using weight alone (P<0.005). A second group of 19 children who underwent technetium-99m DMSA scans, had differential function estimated from both anterior and posterior views and the geometric mean method. The mean difference in differential renal function calculated by the geometric mean method versus the posterior image was only 1.2%. In conclusion, we present a new formula for the estimation of paediatric kidney depth for the absolute quantitation of kidney uptake. Further, for normally located kidneys it appears unnecessary to use the geometric mean method or to correct for individual renal depth when calculating differential function.

Adolescent↗

PubMed1997

Effects of diffusion anisotropy on lesion delineation in a rat model of cerebral ischemia.

The effects of white and gray matter diffusion anisotropy on ischemic lesion delineation have been studied in the rat model of middle cerebral artery occlusion. Apparent diffusion coefficient (ADC) maps obtained by conventional pulsed gradient spin echo diffusion-weighted imaging (PGSE-DWI) were compared with maps of the trace of the diffusion tensor in both normal and occluded animals. Diffusion tensor trace maps were derived from the average of the ADC maps from three separate experiments with diffusion weighting along three orthogonal axes, and also from a single-scan method. A marked degree of diffusion anisotropy was observed in both cortical gray matter and white matter from ADC maps of the control animals. In the occluded animals, the systematic effects of anisotropy on ADC and lesion area influenced the delineation of the ischemic territory in the PGSE-DWI ADC maps. However, the two trace methods eliminated these effects and gave consistent ischemic lesion depiction, despite the use of differing diffusion times in the two measurements.

Animals↗

PubMed1997

Autoradiographic imaging of cerebral ischaemia using a combination of blood flow and hypoxic markers in an animal model.

Current routine clinical techniques, including angiography and perfusional single-photon emission tomography, can be used to indicate problems in cerebral vascular supply and areas of cerebral hypoperfusion following a stroke, but cannot distinguish between ischaemic core and penumbra. In order to image specifically the penumbra, a method or indicator should be able to define areas with reduced blood flow, and a degree of metabolic compromise. In this context, the tissue could be regarded as hypoxic rather than ischaemic, and we have therefore chosen to investigate the potential of radio-labelled hypoxic markers in the study of ischaemia. In order to combine a hypoxic marker with a blood flow marker we used technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) and iodine-125 iodoazomycin arabinoside (125I-IAZA), during cerebral ischaemia in the rat middle cerebral artery occlusion model. 99mTc-HMPAO and 125I-IAZA were injected simultaneously 2 h following occlusion of the middle cerebral artery, and 5 h before decapitation. Paired autoradiograms were produced and compared. Three distinct patterns emerged from the autoradiograms: slightly decreased perfusion with no uptake of the hypoxic marker indicating an area of misery perfusion; moderately decreased perfusion with concomitant uptake of iodoazomycin arabinoside, a region of hypoxia; and severely decreased perfusion with no retention of the hypoxic tracer. In conclusion, we present a new use for an imaging agent in the investigation of cerebral hypoxia. This agent, IAZA together with HMPAO, provides a means of separating the penumbra into regions of misery perfusion and hypoxia. The potential impact of this may be important in the clinical investigation of stroke.

Animals↗

PubMed1997

Development of a radiopharmaceutical activity schedule for technetium-99m dimercaptosuccinic acid in children based on image quality criteria.

The aim of this study was to determine an activity schedule (amount of administered activity in relation to body weight) for technetium-99m dimercaptosuccinic acid examinations in children, from information present in renal scintigraphic images. Scans from 48 children (5 weeks to 14.8 years old) were graded for image quality according to the clarity of both kidney outline and internal structure. Numerical image data (kidney and background counts, signal-to-noise ratio) were associated with these subjective gradings to formulate three criteria, specifying the required values of the above-measured parameters to yield optimum grades of image quality. When applied to derived functions, a kidney uptake of 20% was required to satisfy the criterion based on the signal-to-noise ratio. Using this value with the other two criteria predicts the form of the weight-dependent activity schedule as a function of imaging time. Examples of schedules for imaging times of 300 and 600 s are compared with a schedule based on surface area.

Adolescent↗

PubMed1997

Dosimetry of pediatric radiopharmaceuticals: uniformity of effective dose and a simple aid for its estimation.

UNLABELLED: Formulae were investigated for predicting the effective dose to children, per unit administered activity of various pediatric radiopharmaceuticals, based only on the weight of the patient. Their influence on the uniformity of effective dose from total administered activity was also examined. METHODS: The formulae were obtained from calculations of effective dose per unit administered activity (mSv x MBq[-1]) for five anthropomorphic mathematical phantoms applicable for newborn, 1-yr-, 5-yr-, 10-yr- and 15-yr-old children, having body weights of 3.4, 9.8, 19, 32 and 57 kg, respectively, using published biokinetic models. RESULTS: In general, there was good linear correlation between effective dose per unit administered activity and inverse weight but, for some radiopharmaceuticals, logarithmic regression on weight provided a better fit to the data. An administered activity schedule based on body surface area, used with these formulae, resulted in reasonable uniformity of effective dose for children of all ages, with varying degrees of uniformity for different radiopharmaceuticals (coefficient of variation (COV) up to 20%). Individual activity schedules for separate radiopharmaceuticals gave best uniformity (COV < 7%) while a single general schedule, based on the mean results of the present study, yielded acceptable uniformity (COV < or = 10%) over the pediatric range. CONCLUSION: Effective dose per unit administered activity (mSv x MBq[-1]) of pediatric radiopharmaceuticals can be predicted from body weight alone by using simple formulae, and appropriately choosing the administered activity schedule leads to similar values of effective dose for children of all ages from a given radiopharmaceutical procedure.

Adolescent↗

PubMed1996

Retrospective study of plasma exchange in patients with idiopathic rapidly progressive glomerulonephritis and vasculitis.

A retrospective study of 48 patients was conducted to evaluate the efficacy of plasma exchange in children with idiopathic rapidly progressive glomerulonephritis (IRPGN), and renal or non-renal vasculitis. All patients were followed up at a single centre over a 15 year period. Treatment consisted of corticosteroids and/or cytotoxic agents. Plasma exchange was used in all patients because of severe renal involvement and/or clinical deterioration. One hundred per cent of patients with renal vasculitis who started plasma exchange within one month of disease onset and 58% of cases with IRPGN had significant improvement in renal function. No relapses of vasculitis were observed after treatment with plasma exchange in patients with renal and non-renal vasculitis. The results suggest that plasma exchange associated with immunosuppressive treatment could be of benefit in cases of IRPGN or vasculitis in terms of both renal and extrarenal recovery.

Adolescent↗