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Biomedical subjects

S T Francis

Publications and source records attributed to S T Francis.

10 recordsLinked to original sources

The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people.

Flavanols are the main flavonoids found in cocoa and chocolate, and can be especially abundant in certain cocoas. Research over the past decade has identified flavanols as showing diverse beneficial physiologic and antioxidant effects, particularly in context of vascular function. The present study employed functional magnetic resonance imaging based on blood oxygenation level-dependent (BOLD) contrast to explore the effect of flavanols on the human brain. Magnetic resonance imaging was used to measure BOLD responses to a cognitive task in 16 healthy young subjects. The data presented show an increase in the BOLD signal intensity in response to a cognitive task following ingestion of flavanol-rich cocoa (5 days of 150 mg of cocoa flavanols). This may arise either as a result of altered neuronal activity, or a change in vascular responsiveness, or both--the net effect then being dependent on which of the two effects is dominant. No significant effects were evident in behavioral reaction times, switch cost, and heart rate after consumption of this moderate dose of cocoa flavanols. A pilot study evaluated the relationship between cerebral blood flow and a single acute dose (450 mg flavanols) of flavanol-rich cocoa and showed that flavanol-rich cocoa can increase the cerebral blood flow to gray matter, suggesting the potential of cocoa flavanols for treatment of vascular impairment, including dementia and strokes, and thus for maintaining cardiovascular health.

Adolescent↗

A new quantitative analysis of significant timing differences between externally cued and self-initiated motor tasks in an fMRI study.

It is generally accepted that the temporal resolution of blood oxygenation level dependent functional MRI is limited due to the inherent latency and longevity of the haemodynamic response. However, in this study we introduce a technique for measurement of timing differences from within the same brain region in two (or more) separate tasks that allows accurate determination of cortical timing differences 200 ms. Our technique, based on a novel use of linear regression analysis, is shown to yield accurate results both in simulated and experimental data. We show that cortical timing differences measured using fMRI are consistent with published electrophysiological results. Measurement of timing differences using this technique could prove a useful strategy for identifying neural network components in a wide range of cognitive paradigms.

Algorithms↗

Investigating the BOLD effect during infusion of Gd-DTPA using rapid T2* mapping.

This work aimed to investigate the effects of administering Gd-DTPA on the BOLD effect, and to determine the feasibility of using this approach to measure fractional changes in blood volume and blood oxygenation on neuronal activation during a visual paradigm. A linear relationship between cortical R(2)(*) and the intravascular concentration of Gd-DTPA was demonstrated. The change in R(2)(*) in the visual cortex on activation at 3 T (in the absence of Gd-DTPA) was found to be 1.38 +/- 0.31 s(-1) (N = 4). The fractional change in total blood volume during visual activation was calculated to be 28% +/- 7% (N = 4). The absolute increase in venous blood oxygenation on activation (DeltaY) was estimated to be 21% +/- 4% (N = 4) (assuming HCT = 0.4, resting blood oxygenation = 60%, fraction of volume change that was venous = 36%, and the resting venous fraction of the blood volume = 70%). Simulations showed that the estimated change in venous blood oxygenation was sensitive to the assumed venous blood fraction, and that the estimated fractional change in blood oxygenation was insensitive to whether the change in blood volume occurred in the arterial or venous network.

Adult↗

Measuring the change in CBV upon cortical activation with high temporal resolution using look-locker EPI and Gd-DTPA.

A method of simultaneously measuring the changes in cerebral blood volume (CBV) and T(*) (2) that occur on brain activation with high temporal resolution was developed. The method involves measuring the change in the longitudinal relaxation time (T(1)) that occurs following a bolus injection of Gd-DTPA and converting this measurement to a change in blood volume assuming fast exchange. The sequence was optimized for the measurement of changes in CBV with high temporal resolution. A change in CBV of 27 +/- 4% on activation of the primary visual cortex (V1) was measured across four subjects. The time course of changes in T(*) (2) showed a poststimulus undershoot (P = 0.008) corresponding approximately to a period over which CBV was still elevated above baseline, but falling (P = 0.01). The effects of perfusion, nonfulfillment of the assumption of fast exchange and of intrinsic T(1) changes on activation on the model used to calculate the change in CBV are discussed.

Adult↗

Cortical responses to single mechanoreceptive afferent microstimulation revealed with fMRI.

The technique of intraneural microneurography/microstimulation has been used extensively to study contributions of single, physiologically characterized mechanoreceptive afferents (MRAs) to properties of somatosensory experience in awake human subjects. Its power as a tool for sensory neurophysiology can be greatly enhanced, however, by combining it with functional neuroimaging techniques that permit simultaneous measurement of the associated CNS responses. Here we report its successful adaptation to the environment of a high-field MR scanner. Eight median-nerve MRAs were isolated and characterized in three subjects and microstimulated in conjunction with fMRI at 3.0 T. Hemodynamic responses were observed in every case, and these responses were robust, focal, and physiologically orderly. The combination of fMRI with microstimulation will enable more detailed studies of the representation of the body surface in human somatosensory cortex and further studies of the relationship of that organization to short-term plasticity in the human SI cortical response to natural tactile stimuli. It can also be used to study many additional topics in sensory neurophysiology, such as CNS responses to additional classes of afferents and the effects of stimulus patterning and unimodal/crossmodal attentional manipulations. Finally, it presents unique opportunities to investigate the basic physiology of the BOLD effect and to compare the operating characteristics of fMRI and EEG as human functional neuroimaging modalities in an unusually specific and well-characterized neurophysiological setting.

Brain Mapping↗

fMRI of the responses to vibratory stimulation of digit tips.

Three studies were carried out to assess the applicability of fMRI at 3.0 T to analysis of vibrotaction in humans. A novel piezoelectric device provided clean sinusoidal stimulation at 80 Hz, which was initially applied in separate runs within a scanning session to digits 2 and 5 of the left hand in eight subjects, using a birdcage RF (volume) coil. Significant clusters of activation were found in the primary somatosensory cortex (SI), the secondary somatosensory cortex (SII), subcentral gyrus, the precentral gyrus, posterior insula, posterior parietal regions (area 5), and the posterior cingulate. Digit separation in SI was possible in all subjects and the activation sites reflected the known lateral position of the representation of digit 2 relative to that of digit 5. A second study carried out in six additional subjects using a surface coil, replicated the main contralateral activation patterns detected in study one and further improved the discrimination of the digits in SI. Significant digit separation was also found in SII and in the posterior insula. A third study to investigate the frequency dependence of the response focused on the effect of an increase in vibrotactile frequency from 30 to 80 Hz, with both frequencies applied to digit 2 during the same scanning session in four new subjects. A significant increase in the number of pixels activated within both SII and the posterior insula was found, while the number of pixels activated in SI declined. No significant change in signal intensity with frequencies was found in any of the activated areas.

Adult↗

Continuous saturation EPI with diffusion weighting at 3.0 T.

This paper presents a steady-state method of arterial spin labelling using continuous saturation in conjunction with echo-planar imaging (EPI), which has been implemented at 3 T. The continuous saturation technique has the advantage of having high sensitivity compared to transient labelling techniques, when long repetition times are used. It is also easy to implement and requires minimal data to be acquired for quantitation. Like other arterial spin labelling techniques, continuous saturation is potentially prone to overestimation of perfusion rates due to the effect of tagged blood in vessels within the image slice. Using a simple model of the vasculature, the degree of diffusion weighting required to suppress the arterial signal has been determined, with the results indicating that a value of 2 s/mm2 is adequate. Histogram analysis of the experimental data has been used to evaluate the effect of diffusion weighting. Using a b-value of 2 s/mm2, the mean perfusion-related signal change in grey matter on continuous saturation was found to be 1.5 +/- 0.2%, yielding a mean perfusion rate of 87 +/- 9 ml/100 g/min. Brain activation studies using the diffusion weighted continuous saturation technique gave a mean increase in perfusion of 36 +/- 12% in activated motor cortex.

Arteries↗

Non-invasive mapping of placental perfusion.

BACKGROUND: We aim to develop a clinical technique for the non-invasive measurement of placental perfusion, to enable early detection of intrauterine growth restriction (IUGR). Pregnancies with this complication are characterised by low placental perfusion. METHODS: We measured placental perfusion by means of perfusion-sensitive echoplanar imaging (EPI); a rapid method of making magnetic resonance images. Perfusion measurements were done on six healthy volunteers with normal pregnancies and nine with pregnancies complicated by IUGR. Perfusion maps were created to assess the relation between placental perfusion and fetal size at birth. FINDINGS: Pregnancies complicated by IUGR differed significantly from normal pregnancies in patterns of perfusion within the placenta (p<0.0001, ANOVA). Subsequent analysis showed that the proportion of placentas with low perfusion rates was higher in the IUGR group than in the normal group. A significant correlation between areas of reduced placental perfusion and fetal size was demonstrated (p=0.041, Spearman's rank correlation). INTERPRETATION: Non-invasive imaging of placental perfusion by means of EPI has potential as a clinical tool in assessing the dynamics of placental perfusion.

Echo-Planar Imaging↗

In vivo perfusion measurements in the human placenta using echo planar imaging at 0.5 T.

This paper presents the first in vivo measurements of perfusion in the human placenta from 20 weeks gestational age until term, using the non-selective/selective inversion recovery echo-planar imaging sequence, in which data is alternately acquired following a selective and non-selective inversion pulse. Twenty pairs of images were collected, two each at the following inversion times: 20, 310, 610, 910, 1110, 1410, 1910, 2810, 3310, and 4510 ms with the sequence being repeated with a repetition time (TR) of 10 s. The results of these measurements were used to suggest the optimum sequence for future work in terms of the signal to noise ratio in the measured perfusion rate in a given measurement time. The sequence was also analyzed to determine the expected variability in the measurements. In normal pregnancies the average value of perfusion rate was found to be 176 (standard error = +/-24) ml/100 mg/min. (n = 16, standard deviation = 96 ml/100 mg/min). The expected variability in the measured parameters due to signal to noise ratio considerations alone was calculated to be 71%. For a maximum scanning time of 400 s, the optimum sequence for measuring placental perfusion was found to require 8 repetitions at each of 10 inversion times which were geometrically spaced (given by a(o), a(o)r, a(o)r2, a(o)r3, . . .), with a(o) = 850 ms, r = 1.073 and TR = 5 s, giving a pixel variability of 38%. Other timing schemes are recommended for measuring perfusion in other anatomical regions with different values of perfusion rate and longitudinal relaxation time.

Adult↗

Genetic counselling and gene mutation analysis in familial adenomatous polyposis in Western Australia.

OBJECTIVE: To assess the provision of accurate pre-symptomatic genetic testing with DNA analysis and appropriate counselling for individuals and families known to be at high risk of developing familial adenomatous polyposis coli (FAP). PATIENTS AND METHODS: Thirty-one families with clinically and pathologically documented FAP were ascertained from the Western Australian Polyposis Registry. DNA was collected from over 200 individuals in these families to establish their genetic risk status for FAP, either by direct mutation analysis, or by linkage analysis. Individuals undergoing DNA testing were given intensive psychosocial support and counselling. RESULTS: In 19 families DNA-based counselling could not be offered because either the adenomatous polyposis coli (APC) gene mutation could not be detected or there were insufficient family members for linkage analysis. Gene testing yielded mutations of the APC gene in 87 individuals from 12 families; by gene tracking (or linkage analysis) in three families and by mutation analysis in the remaining nine (four of which had only one affected individual). DNA results conformed with a definite clinicopathological diagnosis in 27 FAP patients and, of the remaining 60 high-risk subjects tested, 14 had inherited the mutated APC gene. CONCLUSIONS: DNA analysis allowed accurate genetic counselling for 12 of 31 families affected by FAP, thus improving the medical and personal management in asymptomatic people who would otherwise be subjected to the uncertainty of long term surveillance and repeated colonic examinations. In future a superior biomolecular approach to gene mutation analysis, such as the protein truncation test, will facilitate management for most FAP individuals and families.

Adenomatous Polyposis Coli↗