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Biomedical subjects

G H Whitehouse

Publications and source records attributed to G H Whitehouse.

At least 19 recordsLinked to original sources

A proton magnetic resonance spectroscopy study of age-related changes in frontal lobe metabolite concentrations.

Ageing is associated with reduction of grey matter volume and it is reported that the frontal lobes are preferentially affected. We have applied quantitative magnetic resonance spectroscopy (MRS), incorporating measurement of brain tissue water content and metabolite T(2) relaxation times, to determine absolute concentrations of the putative neuronal marker N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) compounds in the frontal lobe of 50 male subjects aged between 20 and 70 years (10 per decade). The fractional brain water content (beta(MR)) did not change significantly as a function of age (r = 0.07, P = 0.65) and had a mean value of 81% (CV = 2%). The concentration (in millimoles per litre brain tissue) of NAA decreased significantly with age (r = -0.42, P = 0.003), with an overall decrease of 12% between the third and seventh decades. The concentrations of Cr and Cho did not change significantly with age. The interpretation of the age-dependent decrease in NAA concentration as reflecting either a reduction in neuronal volume, number or function is discussed.

Adult↗

Postprandial decrease in splenic volume demonstrated by magnetic resonance imaging and stereology.

The aim of this study was to determine if the volume of the spleen changes after food intake. We applied an unbiased and efficient method for splenic volume estimation using magnetic resonance imaging (MRI) in combination with modern design stereology. MR images of the spleen were obtained for 10 healthy volunteers (five men and five women; mean age 28.9 years [range 23-35 years]) without a history of splenomegaly. The initial scans were performed in the morning after overnight fasting. Each volunteer then consumed a standard balanced meal weighing 500 g [2,460 kJ (627 kcal) energy] with 500 ml of still mineral water. Second identical MR scans were performed approximately 1 hr later. Postprandially, splenic volume decreased by an average of 6.6% (P = 0.005), probably due to increased splanchnic blood flow after food intake.

Adult↗

Estimation of body composition in muscular dystrophy by MRI and stereology.

We have applied the Cavalieri method of modern design stereology with magnetic resonance imaging for estimating the volume of whole-body muscle and fat compartments in four patients with muscular dystrophy, a patient with myopathy, five controls, an anorexic subject, and a body builder. Detailed systematic series (ie, 50) of axial MR images (T1-weighted, TR/TE 400/10 msec) were obtained throughout the whole body of each subject. The results showed that 15, 20, and 35 axial sections through the body are sufficient to secure coefficients of error (CEs) on the estimates of total muscle and fat volume of around 10%, 5%, and 3% respectively in muscular dystrophy patients and controls. The mean normalized volumes of muscle in four muscular dystrophy patients were decreased by 27% (t-test: P < 0.05), and those of total fat were increased by 12% (t-test: P > 0.05) relative to controls. The Cavalieri method provides a direct, efficient, and mathematically unbiased approach for studying human body compartments and may have application in assessing treatment efficacy in patients with muscular dystrophy. J. Magn. Reson. Imaging 2000;12:467-475.

Adipose Tissue↗

Quantitative magnetic resonance imaging in consecutive patients evaluated for surgical treatment of temporal lobe epilepsy.

We present the results of quantitative Magnetic Resonance Imaging (MRI) in 55 consecutively referred patients with clinical evidence of temporal lobe epilepsy (TLE). The Cavalieri method was used in combination with point counting to provide unbiased estimates of the volume of the left and right hippocampus, amygdala, temporal lobe, lateral ventricles and cerebral hemisphere, and pixel by pixel maps of the T2 relaxation time were computed for both central and anterior sections of the hippocampus. The 99th centiles of hippocampal volume, hippocampal volume asymmetry and T2 relaxation times in 20 control subjects provided limits which identified the presence of MTS. The results of the quantitative MRI were compared with the results of conventional diagnostic MRI, foramen ovale (FO) recording and the WADA test. Thirty-one patients were found to have unilateral MTS (17 left and 14 right) and 7 bilateral MTS. No evidence of MTS was detected in 16 patients. Of the 31 patients diagnosed with unilateral MTS on the basis of hippocampal volume and T2 measurement, 74% and 77% would respectively have received the same diagnosis on the basis of hippocampal volume and T2 measurements alone. In comparison to FO recording, quantitative MRI has a sensitivity of 55% and a specificity of 86%, while conventional diagnostic MRI has a sensitivity of 42% and a specificity of 80% for detection of MTS. Unilateral abnormalities were detected by FO recording in 30% cent of patients who appeared normal on quantitative MRI. WADA test results were available for 40 patients. The findings were consistent with quantitative MRI showing reduced memory function ipsilateral to unilateral MTS in 18 patients, but reduced memory function contralateral to unilateral MTS in two patients, and reduced memory function without MR abnormality in seven patients. WADA testing revealed unilateral memory impairments where MRI found bilateral pathology in 4 patients and in 4 patients in whom quantitative MRI detected unilateral MTS there was no evidence of reduced memory during WADA testing of the corresponding cerebral hemisphere. In the patients with unilateral right MTS a highly significant negative correlation (p = 0.0003) was observed between age of onset and the volume of the contralateral temporal lobe. Quantitative MR imaging of the hippocampus (i.e. volume and T2 measurement) is preferable to conventional radiological reporting for providing objective evidence of the presence of MTS on which to base the referral of patients for surgery, and since it has associated morbidity FO recording is now only being used in selected patients. Furthermore, stereology provides a convenient method for estimating the volume of other brain structures, which is relevant to obtaining a better understanding of the effects of laterality and age of onset of TLE.

Adolescent↗

Magnetic resonance imaging-based compartmentation and its application to measuring metabolite concentrations in the frontal lobe.

Partial volume mixing of water compartments within a spectroscopy voxel (e.g. cerebrospinal fluid within a "brain" voxel) may, if not corrected for, lead to underestimation of brain metabolite concentrations. To correct for this source of bias, a new imaging-based method of compartmentation analysis is presented. Brain water, cerebrospinal fluid and solid matter content were obtained from proton density- and T2-weighted images of the brain and an external standard in 10 healthy young males (21 to 30 years), and results compared with a previously-described technique based on spectroscopy. Mean (SD) fractional water content (betaMR) of the 2 x 2 x 2 cm3 voxel in the frontal lobes was 0.79 (0.03) by imaging, slightly but significantly (p = 0.03) smaller than the value of 0.83 (0.03) obtained by spectroscopy. From water-suppressed spectra recorded at five echo times, using betaMR determined by imaging, the T2-corrected concentrations of compounds containing N-acetylaspartate, creatine, choline and myo-inositol were 10.6 (1.0), 8.0 (0.9), 1.6 (0.3) and 3.7 (0.7) mmol.l(-1) of brain, respectively. Imaging-based compartmentation is a rapid and straightforward technique, and can be performed on standard MR systems.

Adult↗

Structural variation of the distal condyles of the third metacarpal and third metatarsal bones in the horse.

This study examined 3-dimensional (3D) distribution of sectors with contrasting density in the equine third metacarpal (McIII) and third metatarsal (MtIII) bones with a view to explaining the aetiology of distal condylar fractures. Macroradiography and computed tomographic (CT) imaging were used in the nondestructive study of bones obtained from horses, most of which were Thoroughbreds in race training. Distal condylar regions of McIII and MtIII were also studied in microradiographs of 100 microm thick mediolateral sections cut perpendicular to the dorsal and palmar/plantar articular surfaces. Qualitative and quantitative results from all methods used (radiography, CT and microradiographic stereology) demonstrated a densification (sclerosis) of subchondral bone located in the palmar/plantar regions of the medial and lateral condyles of both McIII and MtIII. Substantial density gradients between the denser condyles and the subchondral bone of the sagittal groove were shown to equate with anatomical differences in loading intensity during locomotion. It is hypothesised that such differences in bone density results in stress concentration at the palmar/plantar aspect of the condylar grooves, which may predispose to fracture.

Animals↗

Pathology of the distal condyles of the third metacarpal and third metatarsal bones of the horse.

This study examined material from Thoroughbred horses, the majority of which had been in race training, for evidence of pathology in the third metacarpal (McIII) and third metatarsal (MtIII) bones which might be related to the occurrence of distal condylar fractures. Whole bone samples were studied and documented by macrophotography prior to macroradiography and computed tomographic (CT) imaging. Microradiographs were made from 100 microm thick mediolateral sections cut perpendicular to the dorsal and palmar/plantar articular surfaces of distal condylar regions of McIII and MtIII. Blocks were prepared for morphological imaging using the backscattered electron mode of scanning electron microscopy (BSE SEM). Linear defects in mineralised articular cartilage and subchondral bone were found in the palmar/plantar aspects of the condylar grooves adjacent to the sagittal ridge. These were closely related to the pattern of densification of the subchondral bone and were associated with intense focal remodelling of the immediately adjacent and subjacent bone. Parasagittal fractures of the condyles originated in similar defects. A unifying hypothesis for the aetiopathogenesis of these fractures is presented.

Animals↗

Estimation of breast volume and its variation during the menstrual cycle using MRI and stereology.

Unbiased estimates of breast volume may be obtained in vivo from systematic series of MR images acquired in accordance with the Cavalieri method of modern design-based stereology. The method does not require any assumptions to be made regarding breast shape. If point counting techniques are used to obtain the required breast section areas estimates, 10-15 min analysis (i.e. counting about 250 points on 12 to 16 images) ensures that the contribution of sectioning and point counting to the coefficient of error (CE) on the volume estimate is less than 3%. The methods were applied to measure breast volume in 15 healthy females aged between 22 and 44 years (mean 31.7 years; SD 8.2 years). One subject was studied on every fourth day during two consecutive cycles. The other 14 subjects were studied on three occasions corresponding to menses, ovulation and pre-menses during a single menstrual cycle. Repeat imaging after repositioning on three occasions within a period of 30 min and also at three different times of day for a single subject, both yielded a coefficient of variation (CV) of less than 3% in the estimation of breast volume. ANOVA indicates that there is no significant difference between the mean volume of the left and the right breast (p = 0.294). The mean volume of the left breast is 561 ml (95% confidence interval (CI): 553 ml, 569 ml) and the mean volume of the right breast is 567 ml (95% CI: 559 ml, 576 ml). There are highly significant differences between the three named stages of the menstrual cycle (p < 0.0005), whereby the mean volume at ovulation is 5.5% less than the mean volume at menses (95% CI: 3.0%, 7.9%) and the mean volume pre-menses is 8.1% greater than the mean volume at menses (95% CI: 5.3%, 10.9%). Overall, the volume of each breast varies by an average of 76 ml (95% CI: 61 ml, 92 ml) during the menstrual cycle, which corresponds to 13.6% of the volume at menses (95% CI: 13.3%, 13.8%). No significant interaction was found between the relative volumes of the left and right breast and the stage of the menstrual cycle (p = 0.277), nor between subjects and stages of cycle (p = 0.296). However, a significant interaction was observed between the volume of the left and right breasts in different subjects (p < 0.005). The average difference in the volume of the left and right breasts of all 15 subjects is 39.7 ml (95% CI: 21.3 ml, 58.1 ml), which is 7% of average breast volume and approximately 50% of the average variation in the volume of the breast during the menstrual cycle.

Adult↗

Contrast enhanced dynamic MRI of cervical carcinoma during radiotherapy: early prediction of tumour regression rate.

This prospective study investigated the relationship between changes in the MRI dynamic enhancement of cervical carcinoma early during radiotherapy, and tumour regression rate throughout radiotherapy. A total of 36 MRI examinations was performed in seven patients with cervical carcinoma, including a T2 weighted sequence weekly during radiotherapy and also a multislice dynamic Gd-DTPA enhanced sequence before and after the first 2 weeks of radiotherapy. Tumour enhancement was determined on dynamic images using a region of interest and signal-to-noise ratio method. Serial tumour volumes over time on T2 weighted images were estimated using the Cavalieri method of modern design-based stereology to obtain tumour regression rate. It was found that peak and mean enhancement prior to radiotherapy ranged from 3.0 to 13.3, and from 1.9 to 12.2, respectively. After 2 weeks of radiotherapy, peak and mean enhancement ranged from 7.5 to 13.0, and from 6.3 to 10.6, respectively. The change in peak and mean tumour enhancement between dynamic scans ranged, respectively, from -2.0 to 8.4 and from -4.5 to 8.5. Tumour volume decreased exponentially with time (p < 0.01). Tumour regression rates ranged from 2.0% to 15.2% per day, and correlated positively with changes of both peak and mean tumour enhancement (p < 0.01). It is concluded that MRI dynamic enhancement during the first 2 weeks of radiotherapy may provide early prediction of tumour regression rate, and therefore be of value in designing treatment schedules for cervical carcinoma.

Adult↗

Quantitative analysis of diurnal variation in volume and water content of lumbar intervertebral discs.

The Cavalieri method of modern design stereology has been used in combination with magnetic resonance imaging (MRI) to obtain unbiased estimates of the volume of the lumbar intervertebral discs immediately at the end of a day of normal activity and again following a night's rest. In addition, pixel-by-pixel mapping of the T2-relaxation time has been used to characterize objectively the tissues of the intervertebral discs. The mean increase in height of seven female subjects of average age 21 years (range 19-23 years) measured with a stediometer was 19.3 mm (range 8-26 mm). Image analysis showed that the mean overnight increase in volume of lumbar discs was 1300 mm3 (range 100-2700 mm3). The increase in volume of the disc was accompanied by an increase in the T2-relaxation time of the nucleus pulposus. This suggests that the change in disc volume is most probably caused by a preferential increase in the water content of the nucleus pulposus.

Adult↗

Fetal and fetal brain volume estimation in the third trimester of human pregnancy using gradient echo MR imaging.

The Cavalieri method has been applied in combination with gradient echo magnetic resonance imaging (MRI) to investigate the increase in the volume of the fetus and fetal brain in the third trimester of pregnancy. Eighteen women with singleton pregnancies were recruited. Birthweights for the fetuses all lay within the 10-90th centile based on Liverpool data. A regression analysis, weighted using values derived from the coefficient of error predicted for each volume estimate, revealed a linear relationship between total fetal volume and gestational age (R2 = 0.88) and between fetal brain volume and gestational age (R2 = 0.71) during the third trimester. Fetal volume increased by an average of 25.2 ml per day and fetal brain volume increased by an average of 2.3 mL per day. Fetal brain volume is on average a constant proportion (10%, SD = 2%) of total fetal volume throughout the third trimester. Volume data were also obtained for eight fetuses diagnosed as abnormal. The volume of seven of the eight abnormal fetuses fell outside the 95% confidence interval established from the data obtained for the normal fetuses. However, for only three of the eight abnormal fetuses did brain volume fall outside the 95% confidence interval established for normals, possibly due to brain sparing occurring in asymmetrical growth retardation. The volume of the fetus and fetal brain may be readily estimated directly using the Cavalieri method and magnetic resonance imaging. These parameters represent potentially useful information for assessing fetal growth.

Adult↗

The relationship between the magnetic resonance imaging appearance of the lumbar spine and low back pain, age and occupation in males.

The purpose of this study was to undertake a critical review of the potential role of magnetic resonance imaging (MRI) in the evaluation of low back pain (LBP) and to determine if there were differences in the MRI appearances between various occupational groups. The study group, 149 working men (78 aged 20-30 years and 71 aged 31-58 years) from five different occupations (car production workers, ambulance men, office staff, hospital porters and brewery draymen), underwent MRI of the lumbar spine. Thirty-four percent of the subjects had never experienced LBP. Twelve months later, the examination was repeated on 89 men. Age-related differences were seen in the MRI appearances of the lumbar spine. Disc degeneration was most common at L5/S1 and was significantly more prevalent (P < 0.01) in the older age group (52%) than in the younger age group (27%). Although LBP was more prevalent in the older subjects there was no relationship between LBP and disc degeneration. No differences in the MRI appearance of the lumbar spine were observed between the five occupational groups. Overall, 45% had 'abnormal' lumbar spines (evidence of disc degeneration, disc bulging or protrusion, facet hypertrophy, or nerve root compression). There was not a clear relationship between the MRI appearance of the lumbar spine and LBP. Thirty-two percent of asymptomatic subjects had 'abnormal' lumbar spines and 47% of all the subjects who had experienced LBP had 'normal' lumbar spines. During the 12-month follow-up period, 13 subjects experienced LBP for the first time. However, there was no change in the MRI appearances of their lumbar spines that could account for the onset of LBP. Although MRI is an excellent technique for evaluating the lumbar spine, this study shows that it does not provide a suitable pre-employment screening technique capable of identifying those at risk of LBP.

Absenteeism↗

MRI in the investigation of Morton's neuroma: which sequences?

Morton's 'neuroma' is a painful focus of peri-neural fibrosis, which may affect the interdigital nerves of the feet. Clinical diagnosis and localization may be inaccurate. Computed tomography (CT), ultrasound and magnetic resonance imaging (MRI) have been used to confirm the diagnosis pre-operatively. Recently, MRI using T1-weighted sequences with fat saturation after i.v. Gadolinium DTPA has been suggested as the most effective MR sequence for depiction of Morton's neuroma of the neuroma of the forefoot. Our results show that T1-weighted axial and coronal images with an axial FSE T2-weighted sequence detect neuromata more consistently than an enhanced T1 fat suppressed sequence.

Contrast Media↗

Automatic analysis of cerebral atrophy.

3D MR data obtained for 10 healthy control subjects have been used to build a brain atlas. The atlas is built in four stages. First, a set of features that are unambiguously definable and anatomically relevant need to be computed for each item in the database. The chosen features are crest lines along which the maximal principal curvature of the surface of the brain is maximal in its associated principal direction. Second, a nonrigid registration algorithm is used to determine the common crest lines among the subjects in the database. These crest lines form the structure of the atlas. Third, a set of crest lines is taken as a reference set and a modal analysis is performed to determine the fundamental deformations that are necessary to bring the individual data in line with the reference set. The deformations are averaged and the set of mean crest lines becomes the atlas. Finally, the standard deviation of the deformations between the atlas and the items in the database defines the normal variation in the relative positions of the crest lines in a healthy population. In a fully automatic procedure, the crest lines on the surface of the brain adjacent to the cerebral ventricles in a patient with primary progressive aphasia were compared to the atlas; confirmation that the brain of this patient demonstrates atrophy was provided by stereological analysis that showed that the volume of the left cerebral hemisphere is 48.8 ml (CE 2.8%) less than the volume of the right cerebral hemisphere in the region of the temporal and frontal lobes. When the amplitude of the deformations necessary to register the crest lines obtained for the patient with the atlas were greater than three standard deviations beyond the variability inherent in the atlas, the deformation was considered significant. Four of the main deformation modes of the longest crest line of the surface of the brain adjacent to the cerebral ventricles were significantly different in the patient with primary progressive aphasia compared to the atlas. The ventricles are preferentially enlarged in the left cerebral hemisphere. Furthermore, they are closer together posteriorly and further apart anteriorly than in the atlas. These observations may be indicative of the atrophy of the temporal and frontal lobes of the left cerebral hemisphere noted in the patient. Ultimately, the approach may provide a useful screening technique for identifying brain diseases involving cerebral atrophy. Serial studies of individual patients may provide insights into the processes controlling or affected by particular disease.

Aged↗

Hominid thumb strength predicted by high resolution magnetic resonance imaging and force measurements in living subjects.

This study investigates whether in-vivo measurements of the morphology of the pollical distal phalanx (PDP) can be used to predict the maximum force that can be exerted by the thumb in flexion at the interphalangeal joint. A predictive equation was obtained via which measurements of fossil PDP's can be used to predict flexion force in hominids. A home-built insertable coil assembly, which increased the available magnetic field gradient strength from 10 to 40 (mT) m-1, was used to acquire high resolution T1-weighted 3D SPGR Magnetic Resonance (MR) images of the left and right thumbs of nine volunteers. The subjects' age, sex, weight, height and self-assessed hand-dominance were recorded. The MR images were transferred to a computer for reformatting of sections in the transverse and volar plane (VP). Measurements were made of the maximum length (ML), breadth (MB), tuft breadth (MT) and joint depth (JD) of the PDP. For each subject the maximum flexion force that could be exerted by each thumb was measured. The mean maximum flexion force generated was 8.21 kg (range 5.68-13.13 kg). Considerable inter-individual variability was observed in the magnitude of the force difference between the left and right thumbs and this is greatest in individuals with the strongest thumbs. The best model produced by multiple linear regression analysis of all the available data has a value of r = 0.77 and needs only the two covariates of sex and weight, i.e. FORCE = 2.217 + 0.6651 x WEIGHT + 2.488 x SEX. However, in order to be useful for predicting the maximum flexion force of the thumb in hominids the model should only contain those parameters which can be measured for fossil PDP's. Accordingly, the best predictive model has a value of r = 0.73 and needs only the two covariates of ML and JD, i.e. FORCE = -10.28 + 0.2053 x ML + 1.571 x JD. The maximum force predicted for any of the hominid fossil PDP's was not significantly different from those recorded for the volunteers in the present study, although they were on average somewhat lower than those obtained for modern humans. This may be a reflection of the hominid's overall smaller body weights.

Animals↗

Analysis of cardiac function by MRI and stereology.

Design-based stereology and phase contrast magnetic resonance imaging (MRI) were combined to monitor changes in the volume of the four chambers of the human heart during the cardiac cycle. The data set consisted of 18 adjacent slices (or 'scanning levels') of 0.5 cm thickness, perpendicular to the long axis of the body, and encompassing the whole heart of a healthy volunteer. At each scanning level, a cardiac gated MR image was obtained at each of 16 equally spaced time frames within the cardiac cycle. Given stationarity with respect to time, absence of image artefacts and appropriate definition of chamber boundaries, for each time frame unbiased estimates of total blood volume in the relevant heart chambers were efficiently obtained using the Cavalieri method and point counting. Combined with a proper MRI acquisition, modern stereological methods constitute an efficient and reliable tool to quantify cardiac function noninvasively.

Blood Volume↗