Analysis of dynamic contrast enhanced MRI.
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Biomedical subjects
Publications and source records attributed to A Jackson.
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PURPOSE: To examine the implications of a physiological model of cerebral blood that uses the contradictory assumption that blood flow in all voxels of DSCE-MRI data sets is directional in nature. Analysis of dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSCE-MRI) uses techniques based on indicator dilution theory. Underlying this approach is an assumption that blood flow through pixels of gray and white matter is entirely random in direction. MATERIALS AND METHODS: We have used a directional flow model to estimate theoretical blood flow velocities that would be observed through normal cerebral tissues. Estimates of flow velocities from individual pixels were made by measuring the mean transit time for net flow (nMTT). Measurements of nMTT were made for each voxel by estimating the mean difference in contrast arrival time between each of the adjacent six voxels. RESULTS: Examination of the spatial distribution of contrast arrival time from DSCE-MRI data sets in normal volunteers demonstrated clear evidence of directional flow both in large vessels and in gray and white matter. The mean velocities of blood flow in gray and white matter in 12 normal volunteers were 0.25 +/- 0.013 and 0.21 +/- 0.014 cm/second, respectively, compared to predicted values of 0.25 and 0.18 cm/second. These values give measured nMTT for a 1-mm isotropic voxel of gray and white matter of 0.45 +/- 0.12 and 0.52 +/- 0.11 seconds, respectively, compared to predicted values of 0.47 and 0.55 seconds. CONCLUSION: A directional model of blood flow provides an alternative approach to the calculation of cerebral blood flow from (CBF) DSCE-MRI data.
Oscillations are a widespread feature of normal brain activity and have been reported at a variety of different frequencies in different neuronal systems. The demonstration that oscillatory activity is present in motor command signals has prompted renewed interest in the possible functions of synchronous oscillatory activity within the primate sensorimotor system. In the current study, we investigated task-dependent modulations in coupling between sensorimotor cortical oscillators during a bimanual precision grip task. The task required a hold-ramp-hold pattern of grip force to be exerted on a compliant object with the dominant right hand, while maintaining a steady grip with the nondominant hand. We found significant task-related modulation of 15- to 30-Hz coherence between magnetoencephalographic (MEG) activity recorded from the left sensorimotor cortex and electromyographic (EMG) activity in hand muscles on the right side. This coherence was maximal during steady hold, but disappeared during the ramp movements. Interestingly coherence between the right sensorimotor MEG and left-hand EMG showed a similar, although less deeply modulated, task-related pattern, even though this hand was maintaining a simple steady grip. No significant ipsilateral MEG-EMG coherence was observed in the 15- to 30-Hz passband for either hand. These results suggest that the cortical oscillators in the two sensorimotor cortices are independent to some degree but that they may share a common mechanism that attenuates the cortical power in both hemispheres in the 15- to 30-Hz range during movements of one hand. The results are consistent with the hypothesis that oscillatory activity in the motor system is important in resetting the descending motor commands needed for changes in motor state, such as those that occur in the transition from movement to steady grip.
New developments in fast magnetic resonance imaging (MRI) have enabled imaging of cerebral haemodynamics. This article describes the theory behind perfusion imaging and provides an overview of the most commonly used MRI technique. Limitations of this technique are described, and the potential clinical applications are discussed, with particular attention to the role of perfusion imaging in the context of stroke and brain tumour.
AIM: To determine the optimal collimation, pitch, tube current and reconstruction interval for multi-slice computed tomography (CT) colonography with regard to attaining satisfactory image quality while minimizing patient radiation dose. MATERIALS AND METHODS: Multi-slice CT was performed on plastic, excised pig colon and whole pig phantoms to determine optimal settings. Performance was judged by detection of simulated polyps and statistical measures of the image parameters. Fat and muscle conspicuity was measured from images of dual tube-current prone/supine patient data to derive a measure of tube current effects on tissue contrast. RESULTS: A collimation of 4 x 2.5 mm was sufficient for detection of polyps 4 mm and larger, provided that a reconstruction interval of 1.25 mm was used. A pitch of 1.5 allowed faster scanning and reduced radiation dose without resulting in a loss of important information, i.e. detection of small polyps, when compared with a pitch of 0.75. Tube current and proportional radiation dose could be lowered substantially without deleterious effects on the detection of the air-mucosal interface, however, increased image noise substantially reduced conspicuity of different tissues. CONCLUSION: An optimal image acquisition set-up of 4 x 2.5 mm collimation, reconstruction interval of 1.25 mm, pitch of 1.5 and dual prone/supine scan of 40/100 mA tube current is proposed for our institution for scanning symptomatic patients. Indications are that where CT colonography is used for colonic polyp screening in non-symptomatic patients, a 40 mA tube current could prove satisfactory for both scans.
A patient with an accessory breast on the anterior abdominal wall was found to have cancer of this tissue, because of its unusual position it was decided that lymphatic mapping was necessary to identify the lymphatic drainage of this tumour. A metastasis was found in a sentinel node deep to the 'true' ipsilateral breast; however, the sentinel node identified in the axilla of this patient was free of metastases. The use of the sentinel node technique up staged the cancer from I to II and the patient went on to have adjuvant treatment with chemotherapy. The use of lymphatic mapping and sentinel node biopsy in the case of cancer of an accessory breast allows more accurate determination of lymph node status.
Although several independent studies of gene expression patterns during osteoblast differentiation in cultures from calvaria and other in vitro models have been reported, only a small portion of the mRNAs expressed in osteoblasts have been characterized. We have previously analyzed the behavior of several known markers in osteoblasts, using Affymetrix GeneChip murine probe arrays (27,000 genes). In the present study we report larger groups of transcripts displaying significant expression modulation during the culture of osteoblasts isolated from mice calvaria. The expression profiles of 601 such regulated genes, classified in distinct functional families, are presented and analyzed here. Although some of these genes have previously been shown to play important roles in bone biology, the large majority of them have never been demonstrated to be regulated during osteoblast differentiation. Despite the fact that the precise involvement of these genes in osteoblast differentiation and function needs to be evaluated, the data presented herein will aid in the identification of genes that play a significant role in osteoblasts. This will provide a better understanding of the regulation of osteoblast differentiation and maturation.
Chronic granulomatous disease (CGD) causes growth failure, inflammatory lung damage and often early death. Prophylactic cotrimoxazole improves medium-term survival, but cannot prevent inflammatory sequelae. We report the first patient with CGD who underwent successful HLA identical sibling umbilical cord stem cell transplantation (UCSCT) after myeloablative conditioning. The patient presented with colitis, confirmed as CGD at 2 years of age. Following BU16/CY200 conditioning, he had UCSCT from his unaffected HLA identical sister. A year post-transplant, his colitis had resolved clinically and on radioisotope scan growth has improved. Neutrophil oxidative burst was 92% normal with full donor lymphocyte reconstitution.
OBJECTIVE: To describe the relationship of the mother's physical activity to the birth size of her baby in a rural Indian population. DESIGN: : Prospective observational study. SETTING: Six villages near Pune, Maharashtra, India. SUBJECTS: : A total of 797 women were studied after excluding abortions and termination of pregnancies (112), foetal anomalies (8), multiple pregnancies (3), incomplete pre-pregnancy anthropometry (14) and pregnancies detected later than 21 weeks of gestation (168). METHOD: An activity questionnaire was developed after focus group discussions and incorporated community-specific activities. It was validated against an observer-maintained diary. Activity scores were derived using published data on energy costs to weight the contributions of various activities. It was then administered to assess physical activity at 18 (+/-2) and 28 (+/-2) weeks of gestation. OUTCOME MEASURES: Birth outcome, maternal weight gain and neonatal anthropometry. RESULTS: The activity questionnaire was used to classify women into light, moderate and heavy activity categories. Maternal activity did not influence the incidence of prematurity or stillbirth, or the duration of gestation. It was inversely related to maternal weight gain up to 28 weeks of gestation (P=0.002). Higher maternal activity in early, as well as mid gestation, was associated with lower mean birth weight (P=0.05 and 0.02, respectively ), and smaller neonatal head circumference (P=0.005 and 0.009) and mid-arm circumference (P=0.03 and 0.01) after adjusting for the effect of major confounding factors. CONCLUSIONS: The Findings suggest that excessive maternal activity during pregnancy is associated with smaller foetal size in rural India, The approach described for developing an activity questionnaire has potential for adoption in other settings.
We have assessed the clinical growth index as an indicator of tumour growth rate in 50 patients with a vestibular schwannoma. Clinical growth index was calculated by measuring the length of history and dividing it by the maximum tumour diameter. Total tumour volumes were also measured from all MRI examinations and an effective tumour volume doubling time was calculated. Radiological growth measurements demonstrated involution in 10/50 patients. The median volume doubling time was 1.65 years (range 20.9-46.3 months, skewness 1.72 years). The median clinical growth index was 0.030 cm per month (range 0-0.270 cm per month, skewness 2.398). There was no significant correlation between volume doubling time and clinical growth index. Identification of rapidly growing tumours with clinical growth index >0.025 cm/month had a positive predictive value of 61%, negative predictive value of 48%, false-positive rate of 30% and false-negative rate of 52%. In conclusion, we have shown that the growth rate of vestibular schwannoma is not related to the clinical growth index and we recommend that this measure should be abandoned in the clinical management of patients where conservative management regimes are being considered.
AIM: To determine the accuracy and define the limitations of post mortem magnetic resonance imaging (MRI) in determining the cause of sudden death in adults. METHODS AND RESULTS: Sudden unexpected adult deaths in the community, reported to the Coroner (n = 10), excluding suspicious, violent or potentially drug-related deaths, were submitted to whole body MRI, followed by full invasive autopsy. The MRI scans were reported independently by four radiologists, blinded to the autopsy findings; two had previous experience of post mortem MRI. An abnormality that related to the cause of death as identified at autopsy, was identified by at least one radiologist in eight cases. These were pulmonary consolidation (autopsy finding pneumonia) (n = 1), pneumoperitoneum (autopsy finding perforated peptic ulcer) (n = 2), left ventricular failure (autopsy finding ischaemic heart disease) (n = 4), and disseminated bronchial carcinoma (n = 1). However, in only one case were all radiologists able to provide a confident cause of death (disseminated bronchial carcinoma). In two cases, in which death occurred 2-6 days and 3-6 days before MRI, early decomposition prevented interpretation of the images. Severe coronary artery atheroma was detected at autopsy in 7/10, but these lesions were not detected by MRI. Previous experience in reporting post mortem MRI, without autopsy comparison, did not result in more accurate interpretation of the images. CONCLUSIONS: This pilot study suggests that post mortem MRI can identify some abnormalities relating to the common causes of sudden death in adults, but there is a need for greater experience in correlating MRI with autopsy findings before a reliable cause of death can be made by MRI alone. Inability to image coronary artery lesions, differentiating thrombus from clot and pulmonary oedema from pneumonic exudates, are specific problems that may be corrected with greater experience and higher resolution scans.
The aim was to examine transcriptional and post-transcriptional regulation of LH and FSH biosynthesis. Female cattle were allocated to three groups: (i) Group 1, control (n = 6), synchronized to be at around Day 11 of the oestrous cycle on Day 31; (ii) Group 2 (n = 6), treated with gonadotrophin-releasing hormone (GnRH) agonist (deslorelin) for 31 days; and (iii) Group 3 (n = 6), treated with deslorelin for 28 days. All animals were slaughtered on Day 31. For animals in Group 2, pituitary content of LHbeta-subunit mRNA was suppressed 60% (P < 0.001) and LH 95% (P < 0.001), whereas FSHbeta-subunit mRNA was suppressed 25% (P > 0.05) and FSH 90% (P < 0.001). Three days after treatment with deslorelin (Group 3) LHbeta-subunit mRNA and LH remained suppressed (50% and 95%, respectively; P < 0.001). At the same time, FSHbeta-subunit mRNA did not differ from controls (P > 0.05) whereas FSH remained reduced by 80% (P < 0.001). The ratio of LHbeta-subunit mRNA present in the nucleus versus cytoplasm of gonadotroph cells was reduced (P < 0.05) in heifers during treatment with deslorelin (0.59 +/- 0.05) compared with the ratio in control heifers (1.31 +/- 0.22) and heifers 3 days after discontinuation of treatment (1.01 +/- 0.05). The findings indicated that treatment with GnRH agonist can suppress LHbeta-subunit mRNA expression without any significant effect on FSHbeta-subunit mRNA. As LH and FSH contents were suppressed to a greater degree than their beta-subunit mRNAs, it would appear that treatment with a GnRH agonist might influence gonadotrophin biosynthesis by a post-transcriptional mechanism(s). For LHbeta-subunit mRNA, this would appear not to be reduced export of message from the nucleus.
OBJECTIVE: To determine the levels of sound to which infants are exposed during routine transport by ambulance, aircraft, and helicopter. DESIGN: Sound levels during 38 consecutive journeys from a regional level III neonatal intensive care unit were recorded using a calibrated data logging sound meter (Quest 2900). The meter was set to record "A" weighted slow response integrated sound levels, which emulates the response of the human ear, and "C" weighted response sound levels as a measure of total sound level exposure for all frequencies. The information was downloaded to a computer using MS HyperTerminal. The resulting data were stored, and a graphical profile was generated for each journey using SigmaPlot software. SETTING: Eight journeys involved ambulance transport on country roads, 24 involved fixed wing aircraft, and four were by helicopter. MAIN OUTCOME MEASURES: Relations between decibel levels and events or changes in transport mode were established by correlating the time logged on the sound meter with the standard transport documentation sheet. RESULTS: The highest sound levels were recorded during air transport. However, mean sound levels for all modes of transport exceeded the recommended levels for neonatal intensive care. The maximum sound levels recorded were extremely high at greater than 80 dB in the "A" weighted hearing range and greater than 120 dB in the total frequency range. CONCLUSIONS: This study raises major concerns about the excessive exposure of the sick newborn to sound during transportation.
In studies using single neuron recordings from awake, behaving monkeys, it is necessary to make repeated transdural penetrations using fragile microelectrodes. The tough connective tissue that accumulates after the dura mater is first exposed is often problematic because of electrode breakage and the mechanical stress to the underlying brain tissue caused by excessive dimpling during penetration. We describe the use of an antimitotic compound, 5-fluorouracil (5FU) to control the growth of this connective tissue. 5FU can be safely applied for short periods to the exposed dural tissue on a regular basis provided that it is thoroughly rinsed after application. The advantages of using 5FU are fourfold: first, it depresses fibroblast division and minimizes dural growth and scar tissue formation so that penetrations are easier with less electrode damage or breakage. Second, the frequency of surgical procedures required to remove this tissue are greatly reduced, which benefits both the experiment animal and the experiment. Third, 5FU reduces vascularization of the tissue so that its removal is far easier and without significant blood loss. Finally, 5FU seems to inhibit bacterial infections within the recording chamber. In macaque motor cortex, we performed a quantitative study of electrophysiological data recorded from monkeys with and without 5FU treatment. No significant deleterious side effects produced by 5FU could be detected. Likewise, histological examination of cortical tissue underlying treated dura did not reveal any obvious signs of damage by 5FU. We recommend this approach, with the appropriate safety precautions, to all those neurophysiologists using transdural microelectrode methods in chronically prepared experimental animals. It is also possible that this technique may be useful in other situations where there is dural scarring after surgical intervention or injury.
Tungiasis is caused by the penetration of the female sand flea Tunga penetrans into the epidermis of its host. Human infestation with this ectoparasite is hyper-endemic in many resource-poor communities in sub-Saharan Africa, the Caribbean and South America and is associated with considerable morbidity. Currently, there is no effective drug available to treat tungiasis (or at least none for which a parasiticidal effect has been clearly demonstrated). In an attempt to fill this gap, the effects of treatment with topical ivermectin (lotion), thiabendazole (ointment and lotion), metrifonate (lotion) or placebo lotion were compared in a randomized trial. A total of 108 subjects with 169 tungiasis-infested feet participated in the study. The results show that topical ivermectin, metrifonate or thiabendazole can each significantly reduce the number of lesions caused by embedded sand fleas. Further studies are needed to optimise the doses and administration of these compounds.
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