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Biomedical subjects

H J Wittsack

Publications and source records attributed to H J Wittsack.

14 recordsLinked to original sources

1H-MR spectroscopy, magnetization transfer, and diffusion-weighted imaging in alcoholic and nonalcoholic patients with cirrhosis with hepatic encephalopathy.

PURPOSE: Mild swelling of astrocytes is proposed as a key event in the pathogenesis of hepatic encephalopathy. Proton MR spectroscopy ((1)H-MR spectroscopy), diffusion-weighted imaging (DWI), and magnetization transfer imaging were performed in patients with alcoholic and nonalcoholic liver cirrhosis and correlated with different clinical stages of hepatic encephalopathy to assess alterations in cerebral water metabolism in different subgroups of patients with cirrhosis. MATERIAL AND METHODS: Forty-five patients (26 alcoholics, 19 nonalcoholics [due to hepatitis C (n = 9), hemochromatosis (n = 2), primary chronic cholangitis (n = 2), hepatitis B (n = 1), Wilson disease (n = 1), cryptogenic cirrhosis (n = 4)]) and 18 controls underwent (1)H-MR spectroscopy, magnetization transfer imaging, and DWI of the basal ganglia and normally appearing occipital white matter (NAWM). N-acetylaspartate (NAA), choline (Cho), myo-inositol (mIns), and glutamine/glutamate (Glx) relative to creatine (Cr), the apparent diffusion coefficients (ADC), and the magnetization transfer ratios (MTR) were correlated to the neuropsychologic status, which was assessed by computerized psychometry and mental state grading, according to the West Haven criteria. RESULTS: Compared with controls, nonalcoholic subjects exhibited a gradual increase of Glx/Cr in the basal ganglia and NAWM; a decrease in mIns/Cr; a significant decrease of MTR in the thalamus, the putamen, the pallidum, and NAWM; and an increase in the ADC of the NAWM with increasing hepatic encephalopathy severity. In alcoholics, mIns/Cr of the basal ganglia and the NAWM, Cho/Cr of the basal ganglia, and MTR of all assessed regions were decreased. Glx/Cr of the basal ganglia and of the NAWM was increased, compared with that of controls; but no correlation to the clinical hepatic encephalopathy grading was found. ADC did not change significantly between the groups. CONCLUSIONS: Apart from a typical pattern of (1)H-MR spectroscopy alterations in hepatic encephalopathy, a gradual decrease in MTR and an increase of ADC was found correlating to clinical grading of hepatic encephalopathy in nonalcoholic patients with cirrhosis. In alcoholic patients with hepatic encephalopathy, there was no such correlation. Abnormalities detected by MR imaging may hint at different pathways of brain damage in alcohol-induced liver disease.

Diffusion Magnetic Resonance Imaging↗

[Dynamic contrast-enhanced MRI for evaluating bone marrow microcirculation in malignant hematological diseases before and after thalidomide therapy].

PURPOSE: The aim of the study was to measure microcirculation parameters by dynamic contrast-enhanced MRI (d-MRI) and to evaluate the anti-angiogentic effects during treatment with thalidomide in different hematologic malignancies. METHODS: In 20 healthy normal persons, 20 patients with myelodysplastic syndromes (MDS), 10 patients with multiple myeloma (MM) and 10 with myelofibrosis (MF) a fast gradient echo sequence (Turbo fast low angle shot 2D) with a pump controlled bolus infusion of gadolinium-DTPA was performed before and in 18 of these after beginning (average of 4.3 months) of a thalidomide therapy. Two pharmacokinetic parameters--the amplitude and exchange-rate-constant--were calculated and a statistical comparison of these values between healthy persons and patients as well as a correlation with the clinical course was executed. RESULTS: Compared with the normal controls the patients showed a higher amplitude (normal persons 14.4 +/- 5.2, MDS 24.8 +/- 8.1, MF 35.9 +/- 4.3, MM 23.4 +/- 3.6) and exchange-rate-constant (normal persons 0.124 +/- 0.042, MDS 0.136 +/- 0.036, MF 0.144 +/- 0.068, MM 0.131 +/- 0.034). In the d-MRI-follow-up examinations a significant (p < 0.005) reduction of the amplitude and exchange rate constant values was evident in 14 of 18 patients undergoing a thalidomide therapy. Clinically all of these patients showed a therapy responding with complete or partial diseases remission. CONCLUSIONS: In patients with hematologic malignancies significantly higher d-MRI-microcirculation parameters of the lumbar spine can be demonstrated than in normal persons. During anti-angiogenetic treatment with thalidomide a decrease of these values was observed in case of a responding to therapy.

Adult↗

[Dynamic MRI of the lumbar spine for the evaluation of microcirculation during anti-angiogenetic therapy in patients with myelodysplastic syndromes].

PURPOSE: Evaluation of MRI perfusion parameters of the lumbar spine in patients with myelodysplastic syndromes (MDS) to determine the vascularisation and anti-angiogenetic effects of thalidomide therapy. MATERIAL AND METHODS: In 20 healthy normal persons and 28 MDS patients a dynamic contrast-enhanced MRI (d-MRI) of the lumbar spine was performed. After the initial d-MRI-investigation 24 of the 28 MDS patients received an anti-angiogenetic therapy with thalidomide. With an average of 4.2 months after the beginning of therapy a d-MRI-follow-up examination in 9 of these patients was performed. The amplitude and exchange-rate constant were calculated and a statistical comparison of these values between healthy persons and MDS patients as well as a correlation with the clinical course was executed. RESULTS: Compared with the normal controls the MDS patients showed a higher amplitude (normal persons: 14.4 +/- 5.2, MDS: 24.8 +/- 8.1) and exchange-rate constant (normal persons: 0.124 +/- 0.042, MDS: 0.136 +/- 0.036). In 7 of 9 MDS patients undergoing thalidomide therapy a reduction of the amplitude and exchange rate constant values was evident in the d-MRI follow-up examinations. Clinically these patients showed a therapy response with complete or partial disease remission. CONCLUSIONS: In MDS patients significantly higher d-MRI parameters can be demonstrated than in normal persons. Under anti-angiogenetic treatment these values decrease in case of a response to therapy. Thus, d-MRI seems suitable for the evaluation of anti-angiogenetic therapy effects.

Adult↗

Comparative follow-up of enhancement phenomena with MRI and Proton MR Spectroscopic Imaging after intralesional immunotherapy in glioblastoma--Report of two exceptional cases.

The morphologic pattern of contrast enhancement in magnetic resonance imaging (MRI) of glioblastoma patients could be non specific and metabolic investigations can be useful for the differentiation of tumorous and non tumorous enhancement. Following initial therapy secondary tissue changes can occur and non specific non tumorous enhancement phenomena have been observed after local immuno- and gene therapy strategies. Magnetic resonance spectroscopic imaging (MRSI) has the potential to give more specific information on the metabolism of the suspective tissue and to differentiate enhancing phenomena. We demonstrate two cases of patients suffering from a glioblastoma with simultaneous MRI and MRSI follow-up after multimodal treatment with surgery, radiation, intralesional immunotherapy (IL-4 toxin) and ongoing chemotherapy. MRI demonstrated extensive and increasing enhancement. This was highly suspicious of rapid progressive local tumor recurrency in both patients. Simultaneously obtained MRSI did not show the expected result of extensive and increasing choline concentration within these enhancing areas. This indicated that the enhancement did most likely not reflect vital tumor tissue. Chemotherapy treatment was continued and further MRI follow up revealed nearly complete regression of all enhancement. In pretreated glioblastoma metabolic data of MRSI seem to be potentially helpful to differentiate tumorous and non tumorous enhancement phenomena after local immunotherapy, which might be useful for further treatment decisions.

Adult↗

[User friendly analysis of MR investigations of the cerebral perfusion: Windows(R)-based image processing].

PURPOSE: Quick and user-friendly analysis of perfusion and diffusion weighted MRI by means of interactive computer software. METHOD: A Windows(R)-based software was developed for analysis of perfusion (PWI) and diffusion (DWI) MR imaging. The computer program was developed in the programming language C++ using optimized algorithms, so that a high computing speed on Win95/98/NT systems is achieved. The established SVD algorithms of Østergaard et al. for quantitative perfusion analysis were implemented. RESULTS: Perfusion parameter maps of the cerebral blood flow (rCBF), the mean transit time (MTT) and the cerebral blood volume (rCBV) in consideration of the arterial input function (AIF) can be calculated and visualized using color tables. Additionally, the calculation of "time-to-peak" maps (TTP) and of maps of the percentage change in signal intensity (PC) is possible. The analysis of n = 10 normal persons shows perfusion values that agree with those found in the literature. DISCUSSION: With the computer program developed here color-coded perfusion parameter maps can be calculated easily. Because of the high computing speed it is possible to get information about tissue perfusion on the basis of the large MR data sets even in acute investigations.

Algorithms↗

[Does dynamic contrast-enhanced MRI enable recognition of development of vertebral fractures in multiple myeloma?].

PURPOSE: To compare the value of MRI sequences with dynamic MRI measurements (d-MRT) for the assessment of risk of lumbar vertebral fractures in patients with multiple myeloma. MATERIAL AND METHODS: In 10 patients with multiple myeloma a sagittal T 1 -, T 2 -weighted spin-echo and an inversion-recovery sequence were performed. For dynamic measurements a fast gradient-echo sequence (turbo fast low angle shot 2 D) with machine-controlled Gd-DTPA administration was used. The presence of bone marrow abnormalities was determined and additionally the value of the highest signal increase (amplitude Alpha) was calculated for each of the 50 vertebral bodies. The subsequent development of vertebral fractures was assessed by MRI at a mean time interval of 6.2 months after the initial d-MRI. The pattern of marrow involvement and the amplitudes of the vertebral bodies that collapsed in the observation period were statistically compared with those of the vertebral bodies that did not collapse. RESULTS: During the follow-up period newly or progressive fractures occurred in 6 of 10 patients (7 of 50 vertebral bodies). The degree of pathological signal changes that preceded fractures was not significantly different (p > 0.05) from that of the other contemporary lesions identified in vertebral bodies that did not collapse in follow-up. In contrast, the amplitude of vertebrae that collapsed (A: 33.1 +/- 8.2) was significantly higher (p < 0.0001) than the amplitude of vertebrae that did not collapse (A: 16.7 +/- 4.2). The amplitude was a reliable predictor of vertebrae that collapsed in all cases. CONCLUSION: In contrast to the analysis of marrow lesions detected with non-dynamic MRI, this study suggests that the perfusion-parameter amplitude in dynamic contrast-enhanced MRI is a potentially relevant value to predict the risk of vertebral fractures in patients with multiple myeloma.

Adult↗

Basal ganglia metabolite abnormalities in minor motor disorders associated with human immunodeficiency virus type 1.

BACKGROUND: Minor motor disorders (MMDs) associated with human immunodeficiency virus type 1 (HIV-1) predict HIV-1 dementia and death. Little is known about the time course and neuropathologic mechanisms of HIV-1 MMDs. OBJECTIVE: To investigate the relationship between HIV-1 MMDs, as assessed by psychomotor speed, and metabolic alterations in the basal ganglia, as detected by proton magnetic resonance spectroscopy. PATIENTS AND METHODS: A total of 32 HIV-1-seropositive patients (10 with no MMD, 8 with incipient MMD, and 14 with sustained MMD, assessed through electrophysiologic testing of psychomotor speed including contraction times; 29 treated with highly active antiretroviral therapy) and 14 HIV-1-seronegative control subjects were examined for cerebral metabolite abnormalities in the basal ganglia by means of magnetic resonance spectroscopy. RESULTS: The 3 patient groups showed significantly different ratios of myoinositol/creatine (P =.02) in the basal ganglia. Whereas patients with no MMD or incipient MMD showed normal ratios, patients with sustained MMD showed higher values for myoinositol/creatine as a sign of glial proliferation. No differences in N-acetyl compounds, indicative of neuronal loss, were found. CONCLUSION: Whereas metabolic alterations in the basal ganglia were not detected in patients with incipient HIV-1 MMD, patients with sustained HIV-1 MMD did have significantly altered metabolic spectra indicative of glial proliferation.

AIDS Dementia Complex↗

Proton MR spectroscopy of the lumbar spine in patients with glycogen storage disease type Ib.

Glycogen storage disease type Ib is an autosomal recessive inherited metabolic disorder resulting from deficiency of the microsomal glucose-6-phosphatase enzyme system. Six patients (three of which were treated with granulocyte colony stimulating factor) suffering from this disease were examined using image guided localized proton magnetic resonance (MR) spectroscopy. The relative signal intensities of water and lipid protons of the lumbar spine were determined. Comparison was made with iliac crest biopsies in the glycogen storage disease type Ib patients and localized proton MR spectroscopic values of the lumbar spine obtained by thirteen healthy volunteers. The data demonstrate for the first time that hypercellularity and myeloid hyperplasia in subjects with glycogen storage disease type Ib due to functionally impaired leucocytes results in a strongly increased water proton signal with a very low or absent lipid signal in localized proton MR spectroscopy. Upon granulocyte colony stimulating factor treatment, the water proton signal in the lumbar spine is not further augmented.

Adolescent↗

Treatment of acute basilar artery thrombosis with a combination of systemic alteplase and tirofiban, a nonpeptide platelet glycoprotein IIb/IIIa inhibitor: report of four cases.

In four patients with acute basilar artery thrombosis, complete arterial recanalization and good neurologic outcome were achieved with a treatment combining alteplase with tirofiban. In no cases were cerebral or extracerebral hemorrhagic complications observed. Combined fibrinolytic agents and glycoprotein IIb/IIIa inhibitors may have high potential in the treatment of acute cerebrovascular thrombosis.

Aged↗

Diffusion- and perfusion-weighted MRI in a patient with a prolonged reversible ischaemic neurological deficit.

We report acute and follow-up diffusion- and perfusion-weighted MRI (DWI, PWI) findings in a patient with a prolonged reversible ischaemic neurological deficit. PWI 12 h after the patient was last seen to be without symptoms revealed a large perfusion deficit in the left posterior MCA territory with a relatively inconspicuous and much smaller abnormality on DWI. Follow-up showed resolution of abnormalities on both DWI and PWI, and conventional MRI was normal, apart from a very slight abnormality, visible only on FLAIR images, at the centre of the initially DWI-positive region. These findings demonstrate the utility of PWI when be used in combination with DWI to investigate the pathophysiology of transient ischemic syndromes.

Aged↗

Diffusion- and perfusion-weighted MRI: influence of severe carotid artery stenosis on the DWI/PWI mismatch in acute stroke.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) have been used increasingly in recent years to evaluate acute stroke in the emergency setting. In the present study, we compared DWI and PWI findings in acute stroke patients with and without severe extracranial internal carotid artery (ICA) disease. METHODS: Twenty-seven patients with nonlacunar ischemic stroke were selected for this analysis. DWI, PWI, and conventional MRI were performed in all patients within 24 hours of symptom onset and after 1 week. To exclude patients with partial or complete reperfusion, we included only patients with a PWI deficit larger than the DWI lesion. Severe ICA disease (>70% stenosis) was present unilaterally in 9 and bilaterally in 2 patients. Acute DWI lesion volume, the size of the acute PWI/DWI mismatch, and final infarct size (on T2-weighted images) were determined. RESULTS: The PWI/DWI mismatch was significantly larger in patients with severe ICA disease than in patients without extracranial carotid stenosis, both when time-to-peak and mean transit time maps (P<0.01) were used to calculate the mismatch. Quantitative analysis of the time-to-peak delay in the mismatch indicated that a relatively smaller fraction of the total mismatch was critically ischemic in patients with carotid stenosis than in those without. Average lesion volume increased less in the stenosis group (P=0.14), despite the larger PWI/DWI mismatch, and final infarct size was smaller in the stenosis group (P<0.05). In the 2 patients with bilateral ICA disease, variable hemodynamic involvement of the contralateral hemisphere was found in addition to the ipsilateral PWI deficit. CONCLUSIONS: In most acute stroke patients with severe ICA stenosis, a considerably smaller fraction of the total PWI/DWI mismatch is at risk than in patients without carotid disease.

Acute Disease↗

Diffusion- and perfusion-weighted MRI. The DWI/PWI mismatch region in acute stroke.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) are relatively new MR techniques increasingly used in acute stroke. During the first hours of stroke evolution, the regions with abnormal perfusion are typically larger than the DWI lesions, and this mismatch region has been suggested to be "tissue at risk." The aim of this study was to evaluate the PWI/DWI mismatch region in acute stroke patients and find parameters indicative of both infarct progression and functional impairment. METHODS: Twenty patients with nonlacunar ischemic stroke were imaged with DWI, PWI, and conventional MRI within 24 hours of symptom onset and after 1 week; in addition, the European Stroke Scale (ESS) score was recorded. With PWI, the volumes of regions with "time-to-peak" (TTP) delays of >/=2, 4, 6, 8, and 10 seconds were measured; these volumes were compared with the acute DWI lesion volumes, final infarct size, and ESS score. RESULTS: In 80% of patients the acute DWI lesion was surrounded by regions with abnormal TTP delays (PWI>DWI lesion). A TTP delay of >/=6 s in the mismatch region was found to be associated with lesion enlargement between the initial and follow-up MRI scans. Lesions increased in 9 of 12 patients (75%) in whom the area with TTP delay >/=6 s was larger than the DWI lesion, but they increased in only 1 of 8 (12.5%) of the remaining patients, in whom the area with a TTP delay >/=6 s was smaller than the DWI lesion. The volume of the regions with TTP delays of >/=4 s correlated better with ESS (r=-0.88, P<0.001) than other PWI (or DWI) volumes, which indicated that a TTP delay of approximately 4 s might be the threshold for functional impairment of brain tissue. CONCLUSIONS: Only patients with severe perfusion deficits in the PWI/DWI mismatch (TTP delays of >/=6 s) are at high risk of lesion enlargement. Functionally, more moderate perfusion deficits (TTP delays >/=4 and <6 s) appear to also contribute to the acute clinical deficit.

Acute Disease↗

Absolute metabolite quantification by in vivo NMR spectroscopy: II. A multicentre trial of protocols for in vivo localised proton studies of human brain.

We have performed a multicentre trial to assess the performance of three techniques for absolute quantification of cerebral metabolites using in vivo proton nuclear magnetic resonance (NMR). The techniques included were 1) an internal water standard method, 2) an external standard method based on phantom replacement, and 3) a more sophisticated method incorporating elements of both the internal and external standard approaches, together with compartmental analysis of brain water. Only the internal water standard technique could be readily implemented at all participating sites and gave acceptable precision and interlaboratory reproducibility. This method was insensitive to many of the experimental factors affecting the performance of the alternative techniques, including effects related to loading, standing waves and B1 inhomogeneities; and practical issues of phantom positioning, user expertise and examination duration. However, the internal water standard method assumes a value for the concentration of NMR-visible water within the spectroscopic volume of interest. In general, it is necessary to modify this assumed concentration on the basis of the grey matter, white matter and cerebrospinal fluid (CSF) content of the volume, and the NMR-visible water content of the grey and white matter fractions. Combining data from 11 sites, the concentrations of the principal NMR-visible metabolites in the brains of healthy subjects (age range 20-35 years) determined using the internal water standard method were (mean+/-SD): [NAA]=10.0+/-3.4 mM (n=53), [tCho]=1.9+/-1.0 mM (n=51), [Cr + PCr]=6.5+/-3.7 mM (n=51). Evidence of system instability and other sources of error at some participating sites reinforces the need for rigorous quality assurance in quantitative spectroscopy.

Adult↗

Quantitative measurements with localized 1H MR spectroscopy in children with Canavan's disease.

Canavan's disease is an autosomal recessive hereditary leukodystrophy resulting from deficiency of the enzyme aspartoacylase. Two children suffering from this metabolic brain disease were examined using image-guided localized proton spectroscopy. The absolute concentrations of metabolites were determined. These data demonstrate, for the first time, that the well known increase of the N-acetylaspartic acid (NAA)/Cho ratio in this disease may be not only due to a reduction of choline-containing compounds in brain tissue but, at least in specific cases, also due to an increase of the NAA concentration, which is a result of the enzyme defect.

Aspartic Acid↗