Quality of life and comorbidities in palmoplantar pustulosis - a cross-sectional study on 102 patients.

BACKGROUND: Association of palmoplantar pustulosis (PPP) with metabolic and autoimmune diseases has been reported in mostly small case series or anecdotal cases. OBJECTIVE: To assess health-related quality of life and prevalence of comorbidities in a large cohort of PPP patients. METHODS: We conducted a cross-sectional study on patients with either active or past PPP. Disease severity was measured by the Palmoplantar Pustulosis Area and Severity Index (ppPASI). Quality of life was assessed by the Dermatology Life Quality Index (DLQI). Comorbidities were evaluated by medical history, blood examination, stool testing for Helicobacter pylori antigen and screening tools for depression and psoriatic arthritis. RESULTS: A total of 102 patients (87 women, 15 men) with a mean age of 52.6 ± 14.1 years were evaluated. The mean DLQI was 7 ± 6. Comorbidities were frequent and consisted of hypercholesterolaemia (38%), hypertension (32%), obesity (27%), metabolic syndrome (26%), depression (24%), diabetes (19%), autoimmune thyroiditis (16%) and psoriatic arthritis (16%). CONCLUSION: Patients with PPP have an impaired quality of life and a broad range of comorbidities. Contrary to other reports, our investigation failed to show an association between PPP and coeliac disease or H. pylori infection.

Abatacept (CTLA-4IG) treatment reduces the migratory capacity of monocytes in patients with rheumatoid arthritis.

OBJECTIVE: The binding of abatacept (CTLA-4Ig) to the B7 ligands CD80 and CD86 prevents the engagement of CD28 on T cells and thereby prevents effector T cell activation. In addition, a direct effect of CTLA-4Ig on antigen-presenting cells (APCs) could contribute to the therapeutic effect. To further elucidate the mechanism of CTLA-4Ig, we performed phenotype and functional analyses of APCs in patients with rheumatoid arthritis (RA) before and after the initiation of CTLA-4Ig therapy. METHODS: Peripheral blood mononuclear cells were analyzed before and at 2 and 4 weeks after the initiation of CTLA-4Ig therapy. Proportions of APCs were determined by flow cytometry. CD14+ monocytes were further analyzed for the expression of costimulatory and adhesion molecules and for their transendothelial migratory capacity in vitro. In addition, CD14+ monocytes from healthy controls were analyzed for their migratory and spreading capacity. RESULTS: Proportions and absolute numbers of monocytes were significantly increased in RA patients treated with CTLA-4Ig. The expression of several adhesion molecules was significantly diminished. In addition, monocytes displayed a significant reduction in their endothelial adhesion and transendothelial migratory capacity upon treatment with CTLA-4Ig. Likewise, isolated monocytes from healthy controls revealed a significant reduction in their migratory and spreading activity after preincubation with CTLA-4Ig or anti-CD80 and anti-CD86 antibodies. CONCLUSION: We describe direct effects of CTLA-4Ig therapy on phenotype and functional characteristics of monocytes in RA patients that might interfere with the migration of monocytes to the synovial tissue. This additional mechanism of CTLA-4Ig might contribute to the beneficial effects of CTLA-4Ig treatment in RA patients.

Pristane-induced lupus as a model of human lupus arthritis: evolvement of autoantibodies, internal organ and joint inflammation.

OBJECTIVE: Arthritis is frequently seen in human lupus, but rarely in lupus models. Pristane-induced lupus (PIL) can be induced in various mouse strains such as BALB/c and C57BL/6. We herein characterize clinical and histological features of arthritis in the context of systemic lupus and provide a prudent comparison with models of rheumatoid arthritis (RA). METHODS: A total of 57 BALB/c mice received pristane (PIL group) and were analyzed for serum autoantibodies (anti-chromatin-, -histone, -Sm, -dsDNA), as well as for clinical features and histopathology of joints, lungs and kidneys. Joint pathology was quantified by image analysis and tissue cytometry. Ten C57BL/6 mice (Bl/6-PIL) and historical groups of two different RA models were analyzed accordingly. RESULTS: In BALB/c PIL, clinical arthritis started at three months, occurred finally in 79% of PIL (but not in controls, p<0.001) and correlated with areas of inflammation, erosion, cartilage damage, osteoclast numbers and total severity score (for all: r>0.7, p<0.001). After eight months, 58% of PIL (but no controls, p<0.001) had mild-erosive arthritis. In contrast to RA, the most frequent inflammatory cell type of the pannus was granulocytes (17.7%), PIL had lower numbers of osteoclasts, erosions rarely affected both layers of the cortical bone and there was no progression to complete joint destruction (even after one year of observation). Serum autoantibodies (auto-abs) preceded arthritis and became significantly elevated in all PIL; affected joints showed increased deposits of IgG (and IgM) within the inflammatory tissue, indicative of an ab-mediated process. PIL mice with arthritis also showed signs of pulmonary (100%) and renal (46%) lupus. In contrast to BALB/c, Bl/6-PIL mice did not develop any signs of arthritis. CONCLUSION: PIL in BALB/c mice is characterized by severe organ involvement, typical autoabs and by a mild-erosive arthritis with similarities to, but also with distinct differences from, RA. PIL may help to study arthritis along with other key features of systemic lupus erythematosus after therapeutic interventions or in knock-out models based on a BALB/c but not on a C57BL/6 background.

Effects of Tissue Temperature and Injury on ADC during Therapeutic Hypothermia in Newborn Hypoxic-Ischemic Encephalopathy.

BACKGROUND AND PURPOSE: ADC changes are useful in detecting ischemic brain injury, but mechanisms other than tissue pathology may affect the kinetic movement and diffusion of water molecules. We aimed to determine the effects of brain temperature on the corresponding ADC in infants undergoing therapeutic hypothermia. MATERIALS AND METHODS: Brain temperature and ADC values in the basal ganglia, thalamus, cortical GM, and WM were analyzed during and after therapeutic hypothermia. The study cohort was categorized as having no-injury or injury. Among infants without injury, the correlation between ADC values and temperature was analyzed using the Pearson correlation. Intrasubject comparison of ADC changes during and after therapeutic hypothermia were analyzed, excluding patients who had an MR image interval of >5 days to minimize the effects of injury evolution. RESULTS: Thirty-nine infants with hypoxic-ischemic encephalopathy were enrolled (23 no-injury; 16 injury). The median ADC was significantly lower during therapeutic hypothermia (837; interquartile range, 771-928, versus 906; interquartile range, 844-1032 ×10-6mm2/s; P < .001). There was no difference in the ADC between the no-injury and injury groups during therapeutic hypothermia (823; interquartile range, 782-868, versus 842; interquartile range, 770-1008 ×10-6mm2/s; P = .4). In the no-injury group, in which ADC is presumed least affected by the evolution of injury, the median ADC was significantly lower during therapeutic hypothermia (826; interquartile range, 771-866, versus 897; interquartile range, 846-936 ×10-6mm2/s; P < .001). There was a moderate correlation between temperature and ADC in the no-injury group (during therapeutic hypothermia: Spearman ρ, 0.48; P < .001; after therapeutic hypothermia: ρ, 0.4; P < .001). CONCLUSIONS: Aside from brain injury, reduced tissue temperature may also contribute to diffusion restriction on MR imaging in infants undergoing therapeutic hypothermia.

The First Examination of Diagnostic Performance of Automated Measurement of the Callosal Angle in 1856 Elderly Patients and Volunteers Indicates That 12.4% of Exams Met the Criteria for Possible Normal Pressure Hydrocephalus.

BACKGROUND AND PURPOSE: Many patients with dementia may have comorbid or misdiagnosed normal pressure hydrocephalus, a treatable neurologic disorder. The callosal angle is a validated biomarker for normal pressure hydrocephalus with 93% diagnostic accuracy. Our purpose was to develop and evaluate an algorithm for automatically computing callosal angles from MR images of the brain. MATERIALS AND METHODS: This article reports the results of analyzing callosal angles from 1856 subjects with 5264 MR images from the Open Access Series of Imaging Studies and the Alzheimer's Disease Neuroimaging Initiative databases. Measurement variability was examined between 2 neuroradiologists (n = 50) and between manual and automatic measurements (n = 281); from differences in simulated head orientation; and from real-world changes in patients with multiple examinations (n = 906). We evaluated the effectiveness of the automatic callosal angle to differentiate normal pressure hydrocephalus from Alzheimer disease in a simulated cohort. RESULTS: The algorithm identified that 12.4% of subjects from these carefully screened cohorts had callosal angles of <90°, a published threshold for possible normal pressure hydrocephalus. The intraclass correlation coefficient was 0.97 for agreement between neuroradiologists and 0.90 for agreement between manual and automatic measurement. The method was robust to different head orientations. The median coefficient of variation for repeat examinations was 4.2% (Q1 = 3.1%, Q3 = 5.8%). The simulated classification of normal pressure hydrocephalus versus Alzheimer using the automatic callosal angle had an accuracy, sensitivity, and specificity of 0.87 each. CONCLUSIONS: In even the most pristine research databases, analyses of the callosal angle indicate that some patients may have normal pressure hydrocephalus. The automatic callosal angle measurement can rapidly and objectively screen for normal pressure hydrocephalus in patients who would otherwise be misdiagnosed.

Pediatric Atypical Teratoid/Rhabdoid Tumors of the Brain: Identification of Metabolic Subgroups Using In Vivo 1H-MR Spectroscopy.

BACKGROUND AND PURPOSE: Atypical teratoid/rhabdoid tumors are rare, aggressive central nervous system tumors that are predominantly encountered in very young children. Our aim was to determine whether in vivo metabolic profiles correlate with molecular features of central nervous system pediatric atypical teratoid/rhabdoid tumors. MATERIALS AND METHODS: Twenty confirmed patients with atypical teratoid/rhabdoid tumors who underwent MR spectroscopy were included in this study. In vivo metabolite levels of atypical teratoid/rhabdoid tumors were compared with molecular subtypes assessed by achaete-scute homolog 1 expression. Additionally, brain-specific creatine kinase levels were determined in tissue samples. RESULTS: In vivo creatine concentrations were higher in tumors that demonstrated achaete-scute homolog 1 expression compared with those without achaete-scute homolog 1 expression (3.42 ± 1.1 versus 1.8 ± 0.8 IU, P < .01). Additionally, levels of myo-inositol (mI) (9.0 ± 1.5 versus 4.7 ± 3.6 IU, P < .05) were significantly different, whereas lipids approached significance (44 ± 20 versus 80 ± 30 IU, P = .07) in these 2 cohorts. Higher brain-specific creatine kinase levels were observed in the cohort with achaete-scute homolog 1 expression (P < .05). Pearson correlation analysis showed a significant positive correlation of brain-specific creatine kinase with absolute creatine (P < .05) and myo-inositol (P < .05) concentrations. CONCLUSIONS: In vivo MR spectroscopy may predict key molecular features of atypical teratoid/rhabdoid tumors at initial diagnosis, leading to timely patient risk stratification and accelerating the development of targeted therapies.

Quantitative short echo time 1H-MR spectroscopy of untreated pediatric brain tumors: preoperative diagnosis and characterization.

PURPOSE: Our aims were to evaluate the metabolic profiles of pediatric brain tumors with short echo time (TE) MR spectroscopy and absolute quantitation of metabolite concentrations (in mmol/kg of tissue) and to describe metabolic features that distinguish individual tumor types and that may help to improve preoperative diagnosis of specific tumors. METHODS: MR imaging examinations of 60 patients with untreated brain tumors (14 medulloblastomas, 5 anaplastic astrocytomas, 3 low-grade astrocytomas, 17 pilocytic astrocytomas, 4 anaplastic ependymomas, 5 ependymomas, 3 choroid plexus papillomas, 3 choroid plexus carcinomas, and 6 pineal germinomas) were reviewed. Single-voxel proton MR spectroscopy with a TE of 35 ms was performed and absolute metabolite concentrations were determined by using fully automated quantitation. RESULTS: Taurine (Tau) was significantly elevated in medulloblastomas (P < .00001) compared with all other tumors pooled (All Other). Tau was also observed consistently, at lower concentration, in pineal germinomas. Creatine (Cr) was significantly reduced in pilocytic astrocytomas, distinguishing them from All Other (P < .000001). The MR spectra of choroid plexus papillomas exhibited low Cr (P < .01) concentrations; however, myoinositol was elevated (P < .01) and total choline (tCho) (P < .0001) was reduced relative to All Other. Choroid plexus carcinomas had low Cr (P < .01 versus All Other) and the lowest Cr/tCho ratio (P < .0001 versus All Other) among all tumors studied. Guanidinoacetate was reduced in low-grade astrocytomas and anaplastic astrocytomas (P < .00001) versus All Other, whereas ependymoma and anaplastic ependymomas exhibited particularly low N-acetylaspartate (P < .00001 versus All Other). CONCLUSION: Quantitative proton MR spectroscopy reveals features of pediatric brain tumors that are likely to improve preoperative diagnoses.

Corrigendum to "Developmental synergy between thalamic structure and interhemispheric connectivity in the visual system of preterm infants" [NeuroImage: Clinical 8 (2015) 462-472].

[This corrects the article DOI: 10.1016/j.nicl.2015.05.014.].

Myeloid PTEN deficiency impairs tumor-immune surveillance via immune-checkpoint inhibition.

Tumor-host interaction is determined by constant immune surveillance, characterized by tumor infiltration of myeloid and lymphoid cells. A malfunctioning or diverted immune response promotes tumor growth and metastasis. Recent advances had been made, by treating of certain tumor types, such as melanoma, with T-cell checkpoint inhibitors. This highlights the importance of understanding the molecular mechanisms underlying the crosstalk between tumors and their environment, in particular myeloid and lymphoid cells. Our aim was to study the contribution of the myeloid PI3K/PTEN-signaling pathway in the regulation of tumor-immune surveillance in murine models of cancer. We made use of conditional PTEN-deficient mice, which exhibit sustained activation of the PI3K-signaling axis in a variety of myeloid cell subsets such as macrophages and dendritic cells (DCs). In colitis-associated colon cancer (CAC), mice deficient in myeloid PTEN showed a markedly higher tumor burden and decreased survival. We attributed this observation to the increased presence of immune-modulatory conventional CD8α(+) DCs in the spleen, whereas other relevant myeloid cell subsets were largely unaffected. Notably, we detected enhanced surface expression of PD-L1 and PD-L2 on these DCs. As a consequence, tumoricidal T-cell responses were hampered or redirected. Taken together, our findings indicated an unanticipated role for the PI3K/PTEN-signaling axis in the functional regulation of splenic antigen-presenting cells (APCs). Our data pointed at potential, indirect, tumoricidal effects of subclass-specific PI3K inhibitors, which are currently under clinical investigation for treatment of tumors, via myeloid cell activation.

Oligotide, a defibrotide derivative, protects human microvascular endothelial cells against fludarabine-induced activation, damage and allogenicity.

Fludarabine is a nonmyeloablative immunosuppressant increasingly used as a component of alternative reduced-intensity conditioning regimens prior to allogeneic stem cell transplantation (SCT). However, we have previously shown that 2-fluoroadenine 9-beta-D-arabinofuranoside (F-Ara) as the active metabolized form of fludarabine induces damage, activation and allogenicity in human microvascular endothelial cells (HMEC). We had also identified the pharmaceutic compound Defibrotide (DF), originally used in the treatment of veno-occlusive disease and thrombotic microangiopathy, as being protective against F-Ara-induced dysfunction of HMEC, importantly, without affecting the antileukemic effect of F-Ara. In the present report, we show that a recently developed derivative of DF, Oligotide, similarly downregulates F-Ara-induced activation and damage of HMEC as well as their antigenicity for allogeneic CD8+ T cells. In addition, Oligotide could also block F-Ara-mediated transendothelial migration of peripheral blood cells across the HMEC barrier. Taken together, these observations argue for a potential clinical use of both DF and Oligotide in pre transplant conditioning.

Quantitative proton-decoupled 31P MRS and 1H MRS in the evaluation of Huntington's and Parkinson's diseases.

OBJECTIVE: To determine cerebral energy status in patients with Huntington's disease (HD) and Parkinson's disease (PD). METHODS: The study included 15 patients with DNA-proven, symptomatic HD and five patients with medically treated, idiopathic PD, all of whom were candidates for neurotransplant treatment, as well as 20 age-related normal subjects. Quantitative noninvasive, MRI-guided proton MRS was performed of single volumes in putamen of basal ganglia (BG), occipital gray matter, and posterior parietal white matter; in addition, quantitative phosphorus and proton-decoupled phosphorus MRS of superior biparietal white and gray matter was done. Outcome measures were quantitative metabolite ratios and millimolar concentrations of neuronal and glial markers, creatine (Cr) and adenosine triphosphate (ATP), and intracellular pH. RESULTS: In volume-corrected control BG (10.46 +/- 0.37 mM), [Cr] was 29% (p < 0.05) higher than in control gray matter (8.10 +/- 1.04 mM). In HD and PD, energy metabolism was not abnormal in the four cerebral locations measured by MRS. No increase in cerebral lactate or decrease in phosphocreatine and ATP was detected. Small, systematic abnormalities in N-acetylaspartate (NAA, decreased), Cr (decreased), choline-containing compounds (Cho, increased), and myoinositol (mI, increased) were demonstrable in all patient's individually and in summed spectra but were insufficient to make diagnosis possible in the individual patient. CONCLUSION: Previously described failure of global energy metabolism in HD was not confirmed. However, quantitative 1-hydrogen MRS and decoupled 31-phosphorus MRS are sensitive to +/-10% alterations in key cerebral metabolites, and may be of value in noninvasive monitoring of appropriate therapies.

Improved target volume definition for precision radiotherapy planning of meningiomas by correlation of CT and dynamic, Gd-DTPA-enhanced FLASH MR imaging.

In this methodological paper the authors report a fast, T1-weighted gradient-echo sequence (FLASH) for dynamic, Gd-DTPA-enhanced magnetic resonance (MR) imaging of meningiomas and its application in precision radiotherapy planning. Indications for radiotherapy included unresected tumors, tumor remaining after surgery, and recurrences. The patient's head was fixed in a stereotactic localization system which is usable at the CT, MR and the linear accelerator installations. By phantom measurements different materials (steel, aluminum, titanium, plastic, wood, ceramics) used for the stereotactic system were tested for mechanical stability and geometric MR image distortion. All metallic stereotactic rings (closed rings made of massive metal) led to a more or less dramatic geometric distortion and signal cancellation in the MR images. The best properties--nearly no distortion and high mechanic stability--are provided by a ceramic ring. If necessary, the remaining geometric MR image distortion can be 'corrected' (reducing displacements to the size of a pixel) by calculations based on modeling the distortion as a fourth order two-dimensional polynomial. The target volume was defined in dynamic, T1-weighted FLASH MR images, which were measured before, during, and after the controlled intravenous infusion of 0.1 mmol/kg body weight Gd-DTPA. The stereotactic localization technique allows the precise transfer of the target volume information from MR onto CT data to provide a map of the radiation attenuation coefficient for dose calculation. In genera, the superior soft tissue contrast of MR showed an excellent tumor delineation, especially in regions, such as the base of the skull, where the target often was obscured in CT images.(ABSTRACT TRUNCATED AT 250 WORDS)

Local perfusion and metabolic demand during exercise: a noninvasive MRI method of assessment.

A noninvasive magnetic resonance imaging (MRI) method to assess the distribution of perfusion and metabolic demand (Q/VO(2)) in exercising human skeletal muscle is described. This method combines two MRI techniques that can provide accurate multiple localized measurements of Q/VO(2) during steady-state plantar flexion exercise. The first technique, (31)P chemical shift imaging, permits the acquisition of comparable phosphorus spectra from multiple voxels simultaneously. Because phosphocreatine (PCr) depletion is directly proportional to ATP hydrolysis, its relative depletion can be used as an index of muscle O(2) uptake (VO(2)). The second MRI technique allows the measurement of both spatially and temporally resolved muscle perfusion in vivo by using arterial spin labeling. Promising validity and reliability data are presented for both MRI techniques. Initial results from the combined method provide evidence of a large variation in Q/VO(2), revealing areas of apparent under- and overperfusion for a given metabolic turnover. Analysis of these data in a similar fashion to that employed in the assessment of ventilation-to-perfusion matching in the lungs revealed a similar second moment of the perfusion distribution and PCr distribution on a log scale (log SD(Q) and log SD(PCr)) (0.47). Modeling the effect of variations in log SD(Q) and log SD(PCr) in terms of attainable VO(2), assuming no diffusion limits, indicates that the log SD(Q) and log SD(PCr) would allow only 92% of the target VO(2) to be achieved. This communication documents this novel, noninvasive method for assessing Q/VO(2), and initial data suggest that the mismatch in Q/VO(2) may play a significant role in determining O(2) transport and utilization during exercise.

In vivo quantitation of cerebral metabolite concentrations using natural abundance 13C MRS at 1.5 T.

A method for the quantitation of cerebral metabolites on a clinical MR scanner by natural abundance 13C MRS in vivo is described. Proton-decoupled spectra were acquired with a power deposition within FDA guidelines using a novel coil design. myo-Inositol, quantified by a separate proton MRS, and readily detectable in 13C MRS, was used as an internal reference. Normal concentrations, measured in four control subjects, age 7 months to 12 years, were glutamate 9.9 +/- 0.7, glutamine 5.6 +/- 1.0, and NAA 8.8 +/- 2.8 mmol/kg. In a patient diagnosed with Canavan disease, examined four times, glutamate was reduced to 46% of normal, 4.6 +/- 0.5 mmol/kg. NAA was increased by 50% to 13.2 +/- 1.6 mmol/kg in 13C MRS, consistent with the 41% increase to 12.3 +/- 1.1 from control 8.7 +/- 1.1 mmol/kg assayed by 1H MRS. Limited concentration of glutamate may impact on glutamatergic neurons and excitatory neurotransmission in Canavan disease. Quantitation of cerebral glutamate in human brain may have clinical value in human neuropathologies in which glutamate is believed to play a central role.

Novel peak assignments of in vivo (13)C MRS in human brain at 1.5 T.

(13)C MRS studies at natural abundance and after intravenous 1-(13)C glucose infusion were performed on a 1.5-T clinical scanner in four subjects. Localization to the occipital cortex was achieved by a surface coil. In natural abundance spectra glucose C(3beta,5beta), myo-inositol, glutamate C(1,2,5), glutamine C(1,2,5), N-acetyl-aspartate C(1-4,C=O), creatine CH(2), CH(3), and C(C=N), taurine C(2,3), bicarbonate HCO(-)(3) were identified. After glucose infusion (13)C enrichment of glucose C(1alpha,1beta), glutamate C(1-4), glutamine C(1-4), aspartate C(2,3), N-acetyl-aspartate C(2,3), lactate C(3), alanine C(3), and HCO(-)(3) were observed. The observation of (13)C enrichment of resonances resonating at >150 ppm is an extension of previously published studies and will provide a more precise determination of metabolic rates and substrate decarboxylation in human brain.

MR of hypoxic encephalopathy in children after near drowning: correlation with quantitative proton MR spectroscopy and clinical outcome.

BACKGROUND AND PURPOSE: Quantitative MR spectroscopy has a proved role in the investigation of hypoxia caused by near drowning. To date, no studies have addressed the MR imaging changes that may also accompany this condition. The purpose of this study was to describe the MR imaging findings in children with hypoxic encephalopathy caused by near drowning and to compare these findings with the results of qualitative and quantitative proton MR spectroscopy and clinical outcome. METHODS: Twenty-two children (6 months to 11 years old) admitted to the pediatric intensive care unit after near drowning incidents underwent cerebral MR imaging and quantitative proton MR spectroscopy. Clinical and imaging studies were reviewed retrospectively, and subjects were grouped according to outcome: good result, persistent vegetative state, and death. Images were scored for edema, basal ganglia changes, and cortical changes, and were compared with MR spectra and outcome at days 1 to 2, 3 to 4, and 5 or more. RESULTS: Six patients had a good outcome, four remained in a persistent vegetative state, and 12 died. Generalized/occipital edema correlated with poor outcome. Indistinct lentiform nuclei margins on T1-weighted images were a frequent finding (78%). Basal ganglia T2 hyperintensity correlated with poor outcome, progressing from a patchy/peripheral distribution to diffuse high intensity. Patchy high T2 signal in the cortex or subcortical lines were specific but insensitive for poor outcome, as were brain stem infarcts. CONCLUSION: MR images in children with hypoxic encephalopathy after near drowning show a spectrum of changes. The most sensitive prognostic result may be achieved by combining MR imaging with qualitative and quantitative MR spectroscopic data.

In vivo magnetic resonance spectroscopy of human brain: the biophysical basis of dementia.

Nuclear magnetic resonance spectroscopy (MRS) in low and medium magnetic fields yields well-resolved natural abundance proton and decoupled phosphorus spectra from small (1-10 cc) volumes of brain in vivo in minutes. With this tool, neurochemical research has advanced through identification and non-invasive assay of specific neuronal--(N-acetylaspartate), glial (myo-inositol)--markers, energetics and osmolytes, and neurotransmitters (glutamate, GABA). From these simple measurements, several dozen disease states are recognized, including birth injury, and white matter and Alzheimer disease. Addition of stable isotopes of carbon (in man) or nitrogen (in experimental animals) has provided in vivo assays of enzyme flux through glucose transport, glycolysis, TCA-cycle, and the glutamine-glutamate-GABA system. Finally, a number of xenobiotics are recognized with heteronuclear NMR techniques. Together, these tools are having a major impact on neuroscience and clinical medicine. Through diagnosis and therapeutic monitoring, a new generation of in vivo metabolite imaging is expected with the advent of conforming RF coils and higher field NMR systems.

MR tissue characterization of intracranial tumors by means of texture analysis.

Tissue characterization of the human brain has been performed by texture analysis of proton relaxation time images using a standard MR whole body imager operating at 1.5 T. A combined CP/CPMG multi-echo, multislice sequence was used to measure T1 and T2 in each pixel with an uncertainty not exceeding 10%. In a prospective clinical study, 12 patients with histologically confirmed brain tumors were investigated. For each ROI in the calculated T1 and T2 parameter images, texture parameters originating from the grey level distribution, the gradient distribution, the grey level co-occurrence matrix, and the grey level runlength histogram were used for classification and discrimination between tissues. All regions corresponding to the normal brain tissue (white matter, grey matter, cerebrospinal fluid) were successfully discriminated from each other as well as from the pathological tissue parts (edema and tumor). The classification of 10 edematous and 8 tumorous tissue regions yielded only one misclassification. Together with additional rules, these discrimination rules formed the knowledge base of an expert system for segmentation of the brain images. In cases of tumors without Gd-DTPA contrast medium uptake or in cases of Gd-DTPA contraindication, segmentated images can help solve nontrivial diagnostical problems such as delineating the target volume in radiation therapy.

Radiosurgical treatment planning of brain metastases based on a fast, three-dimensional MR imaging technique.

A fast, three-dimensional (3D) sequence for magnetic resonance (MR) imaging of the brain and its application in radiosurgical treatment planning of brain metastases is reported. The measuring sequence (MPRAGE) requires magnetization-prepared 180 degrees inversion pulses followed by rapid low angle excitation pulses and gradient-echoes for image generation. The resulting T1-weighted MPRAGE images were compared with two-dimensional (2D) T1-weighted spin-echo (SE) images after administration of 0.1 mmol/kg b.w. Gd-DTPA in 10 patients with known brain metastases. Original or multiplanar reformatted images obtained from a 128 partition data set of the 3D MPRAGE sequence offered comparable diagnostic quality to that of 2D SE imaging. Gd-DTPA enhancement and lesion targeting was similar in most of the patients in SE as well as MPRAGE imaging. During imaging and therapy the patient's head was fixed in a stereotactic localization system which is usable at the MR and the linear accelerator installations. The dose calculation of the radiosurgery planning was based on 3D MR imaging data assuming a homogenous attenuation value inside the head which was sufficient for an accurate dose calculation since tissue inhomogeneities do not significantly influence the shape of the relative dose distribution especially for radiosurgery of the brain. Under this circumstance the dose calculation can be based only on the 3D geometric conformation of the patient's head. A simple algorithm for treatment planning can be used if the MR data are free of geometric distortion.(ABSTRACT TRUNCATED AT 250 WORDS)