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Biomedical subjects

W H Backes

Publications and source records attributed to W H Backes.

13 recordsLinked to original sources

Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects.

AIMS/HYPOTHESIS: Mitochondrial dysfunction and increased intramyocellular lipid (IMCL) content have both been implicated in the development of insulin resistance and type 2 diabetes mellitus, but the relative contributions of these two factors in the aetiology of diabetes are unknown. As obesity is an independent determinant of IMCL content, we examined mitochondrial function and IMCL content in overweight type 2 diabetes patients and BMI-matched normoglycaemic controls. METHODS: In 12 overweight type 2 diabetes patients and nine controls with similar BMI (29.4 +/- 1 and 29.3 +/- 0.9 kg/m(2) respectively) in vivo mitochondrial function was determined by measuring phosphocreatine recovery half-time (PCr half-time) immediately after exercise, using phosphorus-31 magnetic resonance spectroscopy. IMCL content was determined by proton magnetic resonance spectroscopic imaging and insulin sensitivity was measured with a hyperinsulinaemic-euglycaemic clamp. RESULTS: The PCr half-time was 45% longer in diabetic patients compared with controls (27.3 +/- 3.5 vs 18.7 +/- 0.9 s, p < 0.05), whereas IMCL content was similar (1.37 +/- 0.30 vs 1.25 +/- 0.22% of the water resonance), and insulin sensitivity was reduced in type 2 diabetes patients (26.0 +/- 2.2 vs 18.9 +/- 2.3 mumol min(-1) kg(-1), p < 0.05 [all mean +/- SEM]). PCr half-time correlated positively with fasting plasma glucose (r (2) = 0.42, p < 0.01) and HbA(1c) (r (2) = 0.48, p < 0.05) in diabetic patients. CONCLUSIONS/INTERPRETATION: The finding that in vivo mitochondrial function is decreased in type 2 diabetes patients compared with controls whereas IMCL content is similar suggests that low mitochondrial function is more strongly associated with insulin resistance and type 2 diabetes than a high IMCL content per se. Whether low mitochondrial function is a cause or consequence of the disease remains to be investigated.

Aged↗

MR angiography of the great anterior radiculomedullary artery (Adamkiewicz artery) validated by digital subtraction angiography.

BACKGROUND AND PURPOSE: Imaging of the anterior superficial spinal cord arteries by MR angiography is hindered by their small calibers and the similarity in configuration with the anterior superficial spinal cord veins. To validate the location and spatial configuration of the great anterior radiculomedullary artery, (ie, the Adamkiewicz artery [AKA]), contrast-enhanced MR angiography (CE-MRA) was compared with digital subtraction angiography (DSA). METHODS: Fifteen patients with suspected spinal cord vascular pathology underwent both spinal CE-MRA and selective spinal DSA. Two phase CE-MRA was performed with the use of a centric k-space filling scheme synchronized to the contrast bolus arrival. The level and side of the AKA origin were scored on the DSA and CE-MRA images and compared regarding image quality in terms of vessel conspicuity, contrast, continuity, sharpness, and background homogeneity on a relative 5-point scale. RESULTS: Localization and spatial configuration of the AKA by CE-MRA was in agreement with DSA findings in 14 of 15 cases. One mismatch of 1 vertebral level (not side) appeared as a result of the tangled vascular pathology. Comparison of image quality revealed that DSA is superior to CE-MRA concerning vessel continuity, sharpness, and background homogeneity (P < .001). Overall vessel conspicuity and contrast were judged to be similar. CONCLUSION: CE-MRA can visualize and localize the level of the AKA correctly. Image quality of CE-MRA is sufficient for detection of the AKA but is inferior to DSA.

Adult↗

MR angiography of the Adamkiewicz artery and anterior radiculomedullary vein: postmortem validation.

SUMMARY: Spinal cord arteries and veins are difficult to visualize and distinguish by MR angiographic techniques because of their small sizes, similar spatial course, and close vascular anatomy. Contrast-enhanced MR angiography was demonstrated to dynamically resolve the Adamkiewicz artery from the anterior radiculomedullary vein in the thoracolumbar spinal cord. The location of the Adamkiewicz artery and the anterior radiculomedullary vein could be validated in the postmortem specimen of a thoracoabdominal aortic aneurysm patient.

Aged↗

Mapping hypercapnia-induced cerebrovascular reactivity using BOLD MRI.

Severe carotid artery stenosis or occlusion may put patients at risk for ischaemic stroke. Reduced cerebrovascular reserve capacity is a possible indicator of an imminent ischaemic event and can be determined by assessment of cerebrovascular reactivity to a vasodilative stimulus. However, little is known about the distribution of cerebrovascular reactivity in healthy individuals. In 13 healthy volunteers, dynamic T2* MR images, acquired at alternating inspiratory pCO2 levels, showed a high percentage of signal change in grey matter, with a strong linear correlation with end-tidal pCO2. The mean percentages of signal change for grey and white matter were 5.9 +/- 1.2% and 1.9 +/- 0.5%, respectively. The mean time lag between CO2 stimulus and haemodynamic response was 15 +/- 4 s for grey matter and 180 +/- 12 s for white matter. Parameter mapping revealed a hemispherically symmetrical and homogeneous distribution of cerebrovascular reactivity over the entire grey matter. These findings indicate that it may be feasible to detect exhausted cerebrovascular autoregulation in patients with a compromised cerebral vasculature.

Adult↗

Dynamic contrast-enhanced magnetic resonance imaging at 1.5 Tesla with gadopentetate dimeglumine to assess the angiostatic effects of anginex in mice.

The purpose of this study was to evaluate the effects of anginex on tumour angiogenesis assessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on a clinical 1.5 Tesla MR system and with the clinically available contrast agent gadopentetate dimeglumine. C57BL/6 mice carrying B16F10 melanomas were treated with anginex, TNP-470 or saline. Tumour growth curves and microvessel density (MVD) were recorded to establish the effects of treatment. DCE-MRI was performed on day 16 after tumour inoculation, and the endothelial transfer coefficients of the microvessel permeability surface-area product (K(PS)) were calculated using a two-compartment model. Both anginex and TNP-470 resulted in smaller tumour volumes (P<0.0001) and lower MVD (P <0.05) compared to saline. Treatment with anginex resulted in a 64% reduction (P<0.01) of tumour K(PS) and TNP-470 resulted in a 44% reduction (P=0.17), compared to saline. DCE-MRI with a clinically available, small-molecular contrast agent can therefore be used to evaluate the angiostatic effects of anginex and TNP-470 on tumour angiogenesis.

Angiogenesis Inhibitors↗

The effects of high field strength MRI on electrodes and pulse generator in dynamic graciloplasty.

OBJECTIVE: Dynamic graciloplasty is a treatment for intractable faecal incontinence. A gracilis muscle is transposed around the anus and stimulated with an implanted pulse generator (IPG). This in vitro study was designed to determine the safety of MRI in patients with implanted electrodes and pulse generators for dynamic graciloplasty. METHODS: Temperatures were measured with fiberoptic probes around the devices in a cadaver model. Current was measured with an oscilloscope connected to electrodes and IPG. Movement and IPG parameter setting were observed before, during and after testing. RESULTS: Minor temperature increase under 1 degrees C were observed around the electrodes. Amplitudes measured were within the range of -1 and +1 Volt. No movement or changing of IPG parameters was noted. CONCLUSION: Changes noted are well within physiological ranges. Dynamic graciloplasty is not a contraindication for high field strength MRI.

Cadaver↗

Usefulness of language and memory testing during intracarotid amobarbital testing: observations from an fMRI study.

BACKGROUND: Several procedures for testing language lateralization and memory function exist during the intracarotid amobarbital test (IAT). The use of functional magnetic resonance imaging (fMRI) gives the opportunity to assess the validity of some of these procedures, or at least to inspect the neuronal correlates. A comprehensive fMRI protocol was tested, aimed at addressing aspects of lateralization of language, as well as testing memory in relation to activation of mesiotemporal regions. Here we report observations with possible consequences for the current IAT procedures. MATERIALS AND METHODS: The protocol consisted of three language tasks (overt naming, semantic decision and silent word generation) and two memory tasks (encoding and retrieving visual scenes). The paradigms used a block-related procedure in nine right-handed normal volunteers. During the procedure dynamic weighted full brain images were acquired which are sensitive to the blood oxygenation activation effect. RESULTS: Encoding showed symmetrical bilateral activation in the mesiotemporal regions, specifically the hippocampus, parahippocampal gyrus and fusiform gyrus. With a retrieval task activation of the mesiotemporal areas was restricted to the posterior hippocampal area. Overt object naming showed results, similar to encoding tasks with bilateral activation of hippocampal areas. Silent word generation showed much stronger ability to lateralize than the other two language-related tasks and especially object naming. CONCLUSION: Activation revealed by fMRI activation shows that IAT procedures, using active semantic language processing or comprehensive procedures with multiple language tasks have the highest guarantee for individual activation lateralization. Simple object naming does not guarantee a lateralized language fMRI activation pattern. Of the different memory procedures during IAT, the procedures (Interview and the Montreal) demanding encoding processing will be related to larger areas of bilateral hippocampal activation than procedures (Seattle) exclusively requiring retrieval. Moreover, tasks using recognition of previously presented language items (naming objects) are equally effective for assessing hippocampal activation compared with presenting separate memory items.

Adult↗

Developing a comprehensive presurgical functional MRI protocol for patients with intractable temporal lobe epilepsy: a pilot study.

Our aim was to put together and test a comprehensive functional MRI (fMRI) protocol which could compete with the intracarotid amytal (IAT) or Wada test for the localisation of language and memory function in patients with intractable temporal lobe epilepsy. The protocol was designed to be performed in under 1 h on a standard 1.5 tesla imager. We used five paradigms to test nine healthy right-handed subjects: complex scene-encoding, picture-naming, reading, word-generation and semantic-decision tasks. The combination of these tasks generated two activation maps related to memory in the mesial temporal lobes, and three language-related maps of activation in a major part of the known language network. The functional maps from the encoding and naming tasks showed typical and symmetrical posterior mesial temporal lobe activation related to memory in all subjects. Only four of nine subjects also showed symmetrical anterior hippocampal activation. Language lateralisation was best with the word generation and reading paradigms and proved possible in all subjects. The reading paradigm enables localisation of language function in the left anterior temporal pole and middle temporal gyrus, areas typically resected during epilepsy surgery. The combined results of this comprehensive f MRI protocol are adequate for a comparative study with the IAT in patients with epilepsy being assessed for surgery.

Adult↗

Simultaneous sampling of event-related BOLD responses in auditory cortex and brainstem.

Event-related functional magnetic resonance imaging (fMRI) was applied to investigate blood oxygen level dependent (BOLD) responses in the human auditory system. Auditory fMRI is hindered by the disturbing acoustical noise of echo planar imaging (EPI). A sparse acquisition technique was used in which the delayed hemodynamic response was imaged at discrete sampling time-points after a brief auditory stimulus. Long repetition times (10 heartbeats (HBs)) were used to avoid interactions between the activation due to the sound stimulation and scanner noise. In addition, only a single slice was acquired, to ensure that the scanner noise was minimal in duration and intensity. The image acquisition was triggered by the HB to prevent artifacts from cardiac-related brainstem motion. An image was acquired every 10th HB. Significant hemodynamic BOLD time-course responses were measured from the primary and secondary auditory cortices, as well as the inferior colliculi in the brainstem. No systematic differences were found between the cerebral cortex and the brainstem in terms of activation amplitude or in onset time of the hemodynamic response. Apparently, the slow dynamic nature of the BOLD response signal is similar across spatially separated auditory brain regions, suggesting a corresponding design of vessels and capillaries.

Acoustic Stimulation↗

Somatosensory cortex responses to median nerve stimulation: fMRI effects of current amplitude and selective attention.

OBJECTIVES: The aim of this study was to localize and to investigate response properties of the primary (SI) and the secondary (SII) somatosensory cortex upon median nerve electrical stimulation. METHODS: Functional magnetic resonance imaging (fMRI) was used to quantify brain activation under different paradigms using electrical median nerve stimulation in healthy right-handed volunteers. In total 11 subjects were studied using two different stimulus current values in the right hand: at motor threshold (I(max)) and at I(min) (1/2 I(max)). In 7 of these 11 subjects a parametric study was then conducted using 4 stimulus intensities (6/6, 5/6, 4/6 and 3/6 I(max)). Finally, in 10 subjects an attention paradigm in which they had to perform a counting task during stimulation with I(min) was done. RESULTS: SI activation increased with current amplitude. SI did not show significant activation during stimulation at I(min). SII activation did not depend on current amplitude. Also the posterior parietal cortex appeared to be activated at I(min). The I(min) response in SII significantly increased by selective attention compared to I(min) without attention. At I(max) significant SI activity was observed only in the contralateral hemisphere, the ipsilateral cerebellum, while other areas possibly showed bilateral activation. CONCLUSIONS: Distributed activation in the human somatosensory cortical system due to median nerve stimulation was observed using fMRI. SI, in contrast to SII, appears to be exclusively activated on the contralateral side of the stimulated hand at I(max), in agreement with the concept of SI's important role in processing of proprioceptive input. Only SII remains significantly activated in case of lower current values, which are likely to exclusively stimulate the sensible fibres mediating cutaneous receptor input. Selective attention only enhances SII activity, indicating a higher-order role for SII in the processing of somatosensory input.

Adult↗

Language activation distributions revealed by fMRI in post-operative epilepsy patients: differences between left- and right-sided resections.

OBJECTIVE: To reveal differences of cerebral activation related to language functions in post-operative temporal lobe epilepsy (TLE) patients. METHODS: Right (RTL) and left temporal lobe (LTL) resected patients, and healthy controls were studied using functional magnetic resonance imaging (fMRI). Only patients with complete left-hemispheric language dominance according to the intracarotid amytal procedure (IAP) were included. Language-related activations were evoked by performing word generation and text reading language tasks. Activation lateralization and temporo-frontal distribution effects were analysed. RESULTS: For word generation, only LTL patients showed reduced left lateralized activation compared to controls, due to a decrease in activation in the left prefrontal cortex and an increase in the right prefrontal cortex. For reading, the left-hemispheric lateralization in RTL patients increased because of enhanced activity in the left prefrontal cortex, whereas for LTL patients the activation became bilaterally distributed over the temporal lobes. Lateralization results between pre-operative IAP and post-operative fMRI were highly discordant. Significant temporo-frontal distribution changes manifested from the reading but not from the word generation task. CONCLUSION: The cerebral language representation in post-operative LTL epilepsy patients is more bi-hemispherically lateralized than in controls and RTL patients. Post-operative temporo-frontal and interhemispheric redistribution effects, involving contralateral homologous brain areas, are suggested to contribute to the cerebral reorganisation of language function.

Adult↗

Functional MR imaging of the cervical spinal cord by use of median nerve stimulation and fist clenching.

BACKGROUND AND PURPOSE: Findings of blood oxygen level-dependent (BOLD) functional MR (fMR) imaging of the cervical spinal cord, obtained by using a fist-clenching motor task, have been sporadically reported. Because spinal activation by sensory stimuli has a potential at least equal to that of fist clenching, its feasibility was assessed. Whether stimulation of the median nerve could evoke an fMR imaging response at 1.5 T in the cervical spinal cord was investigated, and the response pattern was compared with that obtained by fist clenching. METHODS: A dynamic cardiac-gated T2*-weighted imaging sequence was used to quantify cervical spinal cord activation under two paradigms with different numbers of subjects. Seven subjects underwent electrical median nerve stimulation at the elbow sufficient to elicit a maximal compound muscle action potential in the flexor carpi radialis muscle. Eleven subjects performed self-paced fist clenching. Cord activation was measured in the sagittal and transverse imaging planes. RESULTS: In the sagittal view, five of seven subjects had an fMR imaging response in the lower cervical spinal cord upon median nerve stimulation, whereas seven of 11 subjects showed activation with the fist-clenching task. Within the cord, the measured fMR imaging response level was approximately 8-15% with respect to the baseline signal level. In the transverse imaging plane, significant fMR imaging responses could be measured in only two of six and six of nine subjects with median nerve stimulation or fist clenching, respectively. A consistent cross-sectional localization of the activity measured in the spinal cord was not detected, either in terms of the right and left sides or in terms of the posterior and anterior directions. CONCLUSION: In the sagittal plane, median nerve stimulation at the elbow can evoke an fMR imaging response in the lower cervical spinal cord. The activation pattern was comparable with that obtained by fist clenching. The localization of the segmental fMR imaging activation (C4 through T1) is consistent with the known functional neuroanatomy for both paradigms. In the transverse plane, reliable fMR imaging responses were obtained much less frequently, and assignment of distinct areas of the spinal cord to the stimulation methods used was not possible.

Action Potentials↗

Functional MRI of the spinal cord: will it solve the puzzle of pain?

PURPOSE: Whether stimulation of the median nerve could evoke an fMR imaging response at 1.5 T in the cervical spinal cord was investigated and the response pattern was compared with that obtained by fist clenching. METHODS: Eleven subjects performed the fist-clenching task and in seven of them electrical stimulation was also applied. fMRI was performed using a T2* sensitive echo-planar imaging sequence gated by the heartbeat signal. A dynamic cardiac-gated T2*-weighted imaging sequence was used to quantify cervical spinal cord activation. Cord activation was measured in the sagittal and transverse imaging planes. RESULTS: With the fist-clenching task, activation of the spinal cord in the cervical intumescence could be seen in seven of eleven subjects in the sagittal plane and in six of nine subjects in whom axial images were acquired. When median nerve stimulation was applied, cord activation was seen in the sagittal images in five out of seven, and in the axial plane in two out of six subjects. A consistent cross-sectional localization of the activity measured in the spinal cord was not detected, either in terms of the right and left sides or in terms of the posterior and anterior directions. CONCLUSION: In the sagittal plane, median nerve stimulation at the elbow can evoke an fMR imaging response in the lower cervical spinal cord. The activation pattern was comparable with that obtained by fist clenching.

Cervical Vertebrae↗