Graham H. Whitehouse

Estimation of fetal volume by magnetic resonance imaging and stereology

The current methods to monitor fetal growth in utero are based on ultrasound image measurements which, lacking a proper sampling methodology, may be biased to unknown degrees. The Cavalieri method of stereology guarantees the accurate estimation of the volume of an arbitrary object from a few systematic sections. Non-invasive scanning methods, and magnetic resonance imaging (MRI) in particular, are valuable tools to provide the necessary sections, and therefore offer interesting possibilities for unbiased quantification. This paper describes how to estimate fetal volume in utero with a coefficient of error of less than 5% in less than 5 min, from three or four properly sampled MRI scans. MRI was chosen because it does not use ionizing radiations on the one hand, and it offers a good image quality on the other. The impact of potential sources of bias such as fetal motion, chemical shift and partial voluming artefacts is discussed. The methods are illustrated on four subjects monitored between weeks 28 and 40 of gestation.

Measurement of the quadriceps femoris muscle using magnetic resonance and ultrasound imaging.

OBJECTIVES: To define a method for measurement of the cross sectional area and volume of the quadriceps femoris muscle using magnetic resonance imaging (MRI) in conjunction with stereology, and to compare the results of measurements obtained by the MRI method with those obtained by the conventional method of static B-mode ultrasound in order to evaluate whether MRI is a reliable alternative to ultrasound. METHODS: A preliminary MRI study was undertaken on a single female volunteer in order to optimise the scanning technique and sampling design for estimating the muscle volume using the Cavalieri method. Ten healthy volunteers participated in the method comparison study. Each volunteer underwent static B-mode ultrasonography, immediately followed by MRI. The cross sectional area of the quadriceps femoris was estimated at the junction of the proximal one third and distal two thirds of the thigh, and seven systematic sections of the thigh were obtained in order to estimate muscle volume by both modalities. RESULTS: Seven sections through the muscle are required to achieve a coefficient of error of 4-5%. There was no significant difference in the cross sectional area estimates or volume estimates when ultrasound and MRI were compared. CONCLUSION: Muscle cross sectional area and volume can be measured without bias by MRI in conjunction with stereological methods and the method is a reliable alternative to static B-mode ultrasound for this purpose.

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 nights 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. Clin. Anat. 11:1–8, 1998.

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.

The role of magnetic resonance imaging in the assessment of local recurrent breast carcinoma

Experience with magnetic resonance imaging (MRI) of the breast remains limited. MRI studies to date have shown that differentiation of carcinoma from certain benign breast changes can be difficult. The problem of suspected tumour recurrence in patients with known but treated breast carcinoma is considered. Forty-five patients were studied, all having been treated by lumpectomy combined with radiotherapy and/or chemotherapy. Suspicion of recurrence was suggested by X-ray mammography or clinically by the presence of a current breast mass, breast pain, or nipple discharge. The principle differential diagnosis rested between post-treatment fibrosis and recurrent tumour. Axial and sagittal images were obtained using T1-and T2-weighted pulse sequence. Images were enhanced with intravenous gadolinium DTPA in cases where there was a mass. The tomographic format and inherent high soft tissue contrast provided by MRI are of particular value in this situation. The morphological appearances of recurrent tumour, fibrosis, and other post-radiation affects are described and compared. MRI allowed accurate differentiation in the majority of case. In equivocal cases enhancement of mass lesions with gadolinium DTPA provided excellent confirmatory evidence of recurrent tumour.

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.

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.

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.

Normal Variation in the Magnetic Resonance Imaging Appearances of the Sacroiliac Joints: Pitfalls in the Diagnosis of Sacroiliitis

The purpose of this paper is to define the normal and variable appearances of the sacroiliac joints and adjacent subchondral marrow on unenhanced and enhanced Magnetic Resonance Imaging (MRI). Twenty subjects were imaged with spin-echo T1-weighted (T1), fast spin-echo T2-weighted (T2), T1-weighted with fat suppression (T1FS) and fast short tau inversion recovery (Fast STIR) sequences. Five of these subjects were imaged following intravenous Gd-DTPA administration, and the enhancement factor of the synovial compartment of the sacroiliac joint and subchondral marrow was calculated. The appearance of the cartilage of the synovial compartment on T1 and T2 images is of an intermediate signal bounded by signal void of bone cortex. On T1FS and Fast STIR images the cartilage has an intermediate to high signal. The marrow on T1, T2 and T1FS images has a homogeneous intermediate signal. T1FS images demonstrate the synovial compartment with greater clarity than T1 images. Cortical erosions and subchondral sclerosis were not demonstrated in our subjects, and partial volume artifact between the synovial and ligamentous compartments should not be interpreted as erosions. On Fast STIR images there is normally a region of high signal from the immediate subchondral marrow, which should not be interpreted as early sacroiliitis. Seven subjects demonstrated a patchy distribution of fat within the bone marrow, an appearance which alone does not indicate sacroiliitis. One subject had an accessory articular facet of the sacroiliac joint. The percentage maximal enhancement factor of the synovial compartment of the sacroiliac joint and adjacent subchondral marrow is 52% and 94% on T1FS images respectively. These figures redefine the normal maximal enhancement factors in this region of the body.

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.