Magnetization transfer ratio: a quantitative imaging biomarker for 5q spinal muscular atrophy.

BACKGROUND AND PURPOSE: We quantified peripheral nerve lesions in adults with 5q-linked spinal muscular atrophy (SMA) type 3 by analysing the magnetization transfer ratio (MTR) of the sciatic nerve, and tested its potential as a novel biomarker for macromolecular changes. METHODS: Eighteen adults with SMA 3 (50% SMA 3a, 50% SMA 3b) and 18 age-/sex-matched healthy controls prospectively underwent magnetization transfer contrast imaging in a 3-Tesla magnetic resonance scanner. Two axial three-dimensional gradient echo sequences, with and without an off-resonance saturation rapid frequency pulse, were performed at the right distal thigh. Sciatic nerve regions of interest were manually traced on 10 consecutive axial slices in the images generated without off-resonance saturation, and then transferred to corresponding slices generated by the sequence with the off-resonance saturation pulse. Subsequently, MTR and cross-sectional areas (CSAs) of the sciatic nerve were analysed. In addition, detailed neurologic, physiotherapeutic and electrophysiologic examinations were conducted in all patients. RESULTS: Sciatic nerve MTR and CSA reliably differentiated between healthy controls and SMA 3, 3a or 3b. MTR was lower in the SMA 3 (P < 0.0001), SMA 3a (P < 0.0001) and SMA 3b groups (P = 0.0020) than in respective controls. In patients with SMA 3, MTR correlated with all clinical scores, and arm nerve compound motor action potentials (CMAPs). CSA was lower in the SMA 3 (P < 0.0001), SMA 3a (P < 0.0001) and SMA 3b groups (P = 0.0006) than in controls, but did not correlate with clinical scores or electrophysiologic results. CONCLUSIONS: Magnetization transfer ratio is a novel imaging marker that quantifies macromolecular nerve changes in SMA 3, and positively correlates with clinical scores and CMAPs.

Glioma imaging in Europe: A survey of 220 centres and recommendations for best clinical practice.

OBJECTIVES: At a European Society of Neuroradiology (ESNR) Annual Meeting 2015 workshop, commonalities in practice, current controversies and technical hurdles in glioma MRI were discussed. We aimed to formulate guidance on MRI of glioma and determine its feasibility, by seeking information on glioma imaging practices from the European Neuroradiology community. METHODS: Invitations to a structured survey were emailed to ESNR members (n=1,662) and associates (n=6,400), European national radiologists' societies and distributed via social media. RESULTS: Responses were received from 220 institutions (59% academic). Conventional imaging protocols generally include T2w, T2-FLAIR, DWI, and pre- and post-contrast T1w. Perfusion MRI is used widely (85.5%), while spectroscopy seems reserved for specific indications. Reasons for omitting advanced imaging modalities include lack of facility/software, time constraints and no requests. Early postoperative MRI is routinely carried out by 74% within 24-72 h, but only 17% report a percent measure of resection. For follow-up, most sites (60%) issue qualitative reports, while 27% report an assessment according to the RANO criteria. A minority of sites use a reporting template (23%). CONCLUSION: Clinical best practice recommendations for glioma imaging assessment are proposed and the current role of advanced MRI modalities in routine use is addressed. KEY POINTS: • We recommend the EORTC-NBTS protocol as the clinical standard glioma protocol. • Perfusion MRI is recommended for diagnosis and follow-up of glioma. • Use of advanced imaging could be promoted with increased education activities. • Most response assessment is currently performed qualitatively. • Reporting templates are not widely used, and could facilitate standardisation.

SLC6A4 gene variants moderate associations between childhood food insecurity and adolescent mental health.

BACKGROUND: Food insecurity is a persistent concern in the United States and has been shown to affect child mental health and behavior. The SLC6A4 gene has been indicated as a moderator of the effects of chronic stress on anxiety in adolescents aged 14-21. However, it is unclear if SLC6A4 may also play a role in the effects of childhood food insecurity, a form of chronic stress, on adolescent mental health. This study aimed to identify effects of food insecurity on adolescents' mental health and delinquent behavior when both mom and child go hungry in the child's early years, and the potential interaction with SLC6A4 variants (SS/LL). METHODS: The data and sample for this research are from the Future of Families and Child Wellbeing Study. The cohort consists of 4898 children (age 1-15 years, male = 47%, African American = 50%) and their respective caregivers sampled from large cities in the United States from 1998 to 2000. RESULTS: The SLC6A4 serotonin transporter short/short allele emerged statistically significant as a moderator of childhood food insecurity and adolescent mental health. Specifically, the presence of the short/short allele increased anxiety symptoms in adolescents with exposure to food insecurity in childhood. CONCLUSION: The SLC6A4 short/short allele amplifies risk of anxiety-related mental illness when children experience food insecurity. The gene-environment interaction provides insight into the mechanistic pathway of the effects of poverty-related adversity, such as food insecurity, on developmental trajectories of mental health.

3-T contrast-enhanced MR angiography with parallel imaging in cerebral venous and sinus thrombosis.

BACKGROUND AND PURPOSE: Contrast-enhanced (CE) 3D magnetic resonance venography (MRV) and CE 3D magnetization prepared rapid acquisition of gradient echo (MP-RAGE) sequences are increasingly commonly used methods for evaluation of the intracranial venous system. Our aim was to compare CE MRV, 2D time-of-flight (TOF) MRV and MP-RAGE sequences at 3 T for visualization of cerebral venous and sinus thrombosis. MATERIAL AND METHODS: Patients with suspected or known cerebral venous thrombosis were examined prospectively by TOF MRV, CE MRV and MP-RAGE sequences. In 11 consecutive patients (all women; mean age, 42.5 years; age range, 25-70 years) with venous thrombosis, scores according to overall image quality, and presence or absence (score P) and differentiation (score D) of venous thrombosis were evaluated. RESULTS: By all measurements, overall image quality ranged from good to excellent. In 20 of 52 venous structures (38.5%), score P was the same on TOF MRV, CE MRV and MP-RAGE sequences. Venous thrombosis was definitely or almost definitely present or absent with TOF MRV in 20 of 52 (38.5%), with CE MRV in 97 of 99 (97.9%) and with MP-RAGE sequences in 86 of 99 (86.9%) venous structures. In all venous structures with uncertain diagnosis on TOF MRV, thrombosis was definitely or almost definitely present or absent on CE MRV and MP-RAGE sequences. Differentiation of thrombosis was better on CE MRV (score D: 3.33) than on MP-RAGE sequences (score D: 2.78), followed by TOF MRV (score D: 1.32). CONCLUSION: CE MRV was superior to TOF MRV and MP-RAGE sequences in visualizing cerebral venous and sinus thrombosis.

Diffusion tensor imaging MR Neurography detects polyneuropathy in type 2 diabetes.

AIM: To evaluate if diffusion-tensor-imaging MR-Neurography (DTI-MRN) can detect lesions of peripheral nerves due to polyneuropathy in patients with type 2 diabetes. METHODS: Ten patients with type 2 diabetes with polyneuropathy (DPN), 10 patients with type 2 diabetes without polyneuropathy (nDPN) as well as 20 healthy controls (HC) were included. DTI-MRN covered proximal (sciatic nerve) and distal regions (tibial nerve) of the lower extremity. Fractional-anisotropy (FA) and diffusivity (mean (MD), axial (AD) and radial (RD)) were calculated and compared to neuropathy severity. Conventional T2-relaxation-time and proton-spin-density data were obtained from a multi-echo SE sequence. Furthermore, we evaluated sensitivity and specificity of DTI-MRN from receiver operating characteristics (ROC). RESULTS: The proximal and distal FA was lowest in patients with DPN compared with nDPN and HC (p < 0.01). Likewise, proximal and distal RD was highest in patients with DPN (p < 0.01). MD and AD were also significantly different though less pronounced. ROC curve analyses of DTI separated nDPN and DPN with area-under-the-curve values ranging from 0.65 to 0.98. T2-relaxation-time and proton-spin-density could not differentiate between nDPN and DPN. CONCLUSION: DTI-MRN accurately detects DPN by lower nerve FA and higher RD. These alterations are likely to reflect both proximal and distal nerve fiber pathology in patients with type 2 diabetes.

DTI of commissural fibers in patients with Chiari II-malformation.

Chiari II-malformation is a complex congenital deformity of the brain which is frequently associated with hydrocephalus. Abnormalities of the corpus callosum are known to occur in the majority of patients. The objective of the present study was to study the microstructure of the corpus callosum (CC) and the anterior commissure (AC) to differentiate between different mechanisms of damage to these structures. We investigated 6 patients with Chiari II-malformation and 6 well-matched healthy volunteers employing T1-weighted 3D imaging and diffusion tensor imaging (DTI) to determine the fractional anisotropy (FA) and cross-sectional area of the CC and AC, as well as with neuropsychological testing. Four patients showed hydrocephalus, two patients had callosal dysplasia and four had a hypoplastic CC. The callosal FA in the patients was significantly reduced which was less pronounced for the genu alone. The area of CC was also reduced in Chiari II-patients. There was a strong correlation between the size and FA of the CC in the patients. In contrast, the thickness of the AC was significantly increased and was associated with higher FA in the patients. In psychological tests all patients showed reduced verbal memory; all but one patient showed reduced IQ as well as impaired visuo-spatial performance, indicating deficits in tasks requiring parieto-occipital integration. The existence of callosal dysplasia in two patients, the diminished FA reduction in the genu and the correlation of the cross-sectional area and FA in the patients point to a developmental white matter damage beside that exerted by hydrocephalus alone.

Fiber tracking of human brain using fourth-order tensor and high angular resolution diffusion imaging.

The accuracy of fiber tracking on the basis of diffusion tensor magnetic resonance imaging (DTI) is affected by many parameters. To increase accuracy of the tracking algorithm, we introduce DTI with a fourth-order tensor. Tensor elements comprise information obtained by high angular resolution diffusion imaging (HARDI). We further developed the flattened high rank tensor (FLAHRT) method and applied it to the measured fourth-order tensor. We then compared FLAHRT with: 1) the standard tracking algorithm using a second-order tensor; and 2) existing techniques involving the representation of conventional second-order tensor components as a weighted average of fourth-order tensor elements. Such techniques have been formulated in recent DT studies to link high-rank to low-rank Cartesian diffusion tensors (DTs). Diagonalization of the second-order tensor decomposes the tensor into three eigenvalues and three eigenvectors, which in turn are used to describe the diffusivity profile of a particular voxel. Diagonalization after application of the FLAHRT method reveals six eigenvalues and six eigentensors, resulting in a more accurate description of the anisotropy. We performed fiber tracking based on the eigenvalues and eigentensors calculated with the FLAHRT and standard methods. We could show that the FLAHRT technique gives more consistent and more accurate results even with a data set acquired in 15 directions only. The decomposition of the fourth-order tensor into six eigentensors has the potential to describe six different fiber orientations within a voxel.

Prospective combined brain and spinal cord MRI in clinically isolated syndromes and possible early multiple sclerosis: impact on dissemination in space and time.

BACKGROUND: The diagnosis of multiple sclerosis (MS) is based on dissemination in space (DIS) and time (DIT). The aim of the study was to assess the impact of spinal cord (SC) imaging on the evidence of DIS and DIT. METHODS: Thirty-five treatment-naive patients with a first clinical symptom suggestive of MS were examined in a 2-year prospective longitudinal follow-up assessment. Brain and SC magnetic resonance imaging (MRI), Expanded Disability Status Scale and multiple sclerosis functional composite were analysed at baseline and after 1 and 2 years. RESULTS: At study entry, 21 patients were classified as clinically isolated syndrome suggestive of MS (CIS) and 14 patients as possible early MS. SC lesions were detected at baseline in 14 CIS patients (67%, median: 1.0, enhancing 29%) and in 11 patients with possible early MS (79%, median: 2.0, enhancing 29%). DIS as depicted by additive SC imaging was detected in two additional individuals according to the revised versus the 2001 McDonald criteria. All patients with emerging cord lesions showed new brain lesions. Five individuals developed clinically asymptomatic cord lesions. CONCLUSIONS: Spinal cord abnormalities are frequent in CIS patients and in patients with possible early MS. SC imaging slightly improved the establishment of DIS, but had no impact on the evidence of DIT.

[Impact of technical and morphological factors on the precision of software-based MR tumor volumetry: a phantom study]. / Einfluss messtechnischer und morphologischer Faktoren auf die Genauigkeit der softwarebasierten MR-Tumorvolumetrie: eine Phantomstudie.

PURPOSE: To investigate the impact of technical and morphological parameters on the precision of software-based MR tumor volumetry (SBV) in an in-vitro experimental setting. MATERIALS AND METHODS: Tumor models were formed from a silicone compound in three different sizes with a max. diameter < 2 cm (small), 2 - 4 cm (middle), and > 4 cm (large). For each size a spherical, an elliptic and an irregular shaped model was produced. The true volume of the tumor models was established by water displacement. Tumor models were examined with a high-field MRI (TRIO, 3 Tesla, Siemens) with T 2-weighted sequences under optimized contrast conditions. Slice thickness was 1, 3 and 5 mm. The volume of the tumor models was then calculated using (1). manually driven volumetric software (SBVmanual) and (2). automatic volumetric software (SBVauto). The influence of the following parameters on the precision of SBV was analyzed: Size and shape of the tumor models, manual/automatic SBV, segmentation technique and slice thickness. RESULTS: In general, SBVauto measurements showed less deviation than measurements with SBVmanual (p < 0.01). However, both methods depended significantly on morphologic factors, especially on tumor size. In small tumor models, the volume was strongly underestimated by -36.2 +/- 27.8 % (SBVmanual) and -33.1 +/- 8.6 % (SBVauto), whereas the deviation for large tumor models was only 2.0 +/- 14.7 % (SBVmanual) and 3.0 +/- 2.3 % (SBVauto; p < 0.01). The deviation of measurements increased from the "spherical" to the "irregular" shape by 9.5 % (SBVmanual) and 10.7 % (SBVauto). In addition, SBVmanual depended on technical factors. Using a "minimal" segmentation technique (e. g. excluding partial volume effects), volumes were underestimated in all cases, whereas volumes of middle and large tumor models were slightly overestimated when using a "maximum" segmentation technique (e. g. including partial volume effects; p = 0.01). Deviation of SBVmanual increased with slice thickness from 15.9 +/- 12.7 % (1 mm slices) to 27.1 +/- 21.3 % (5 mm-slices). CONCLUSION: In general, SBVauto measurements yielded smaller deviations than SBVmanual. However, both methods showed major inaccuracy in the volumetric estimation of small and irregular shaped tumor models, thus the tumor volumetry of these tumors has to be considered inappropriate for clinical practice. Moreover, the exactness of SBVmanual depended significantly on segmentation technique and slice thickness.

Diffusion effects in myelin sheath free induction decay.

Myelin sheath microstructure and composition produce MR signal decay characteristics that can be used to evaluate status and outcome of demyelinating disease. We extend a recently proposed model of neuronal magnetic susceptibility, that accounts for both the structural and inherent anisotropy of the myelin sheath, by including the whole dynamic range of diffusion effects. The respective Bloch-Torrey equation for local spin dephasing is solved with a uniformly convergent perturbation expansion method, and the resulting magnetization decay is validated with a numerical solution based on a finite difference method. We show that a variation of diffusion strengths can lead to substantially different MR signal decay curves. Our results may be used to adjust or control simulations for water diffusion in neuronal structures.

MSVAT-SPACE-STIR and SEMAC-STIR for Reduction of Metallic Artifacts in 3T Head and Neck MRI.

BACKGROUND AND PURPOSE: The incidence of metallic dental restorations and implants is increasing, and head and neck MR imaging is becoming challenging regarding artifacts. Our aim was to evaluate whether multiple-slab acquisition with view angle tilting gradient based on a sampling perfection with application-optimized contrasts by using different flip angle evolution (MSVAT-SPACE)-STIR and slice-encoding for metal artifact correction (SEMAC)-STIR are beneficial regarding artifact suppression compared with the SPACE-STIR and TSE-STIR in vitro and in vivo. MATERIALS AND METHODS: At 3T, 3D artifacts of 2 dental implants, supporting different single crowns, were evaluated. Image quality was evaluated quantitatively (normalized signal-to-noise ratio) and qualitatively (2 reads by 2 blinded radiologists). Feasibility was tested in vivo in 5 volunteers and 5 patients, respectively. RESULTS: Maximum achievable resolution and the normalized signal-to-noise ratio of MSVAT-SPACE-STIR were higher compared with SEMAC-STIR. Performance in terms of artifact correction was dependent on the material composition. For highly paramagnetic materials, SEMAC-STIR was superior to MSVAT-SPACE-STIR (27.8% smaller artifact volume) and TSE-STIR (93.2% less slice distortion). However, MSVAT-SPACE-STIR reduced the artifact size compared with SPACE-STIR by 71.5%. For low-paramagnetic materials, MSVAT-SPACE-STIR performed as well as SEMAC-STIR. Furthermore, MSVAT-SPACE-STIR decreased artifact volume by 69.5% compared with SPACE-STIR. The image quality of all sequences did not differ systematically. In vivo results were comparable with in vitro results. CONCLUSIONS: Regarding susceptibility artifacts and acquisition time, MSVAT-SPACE-STIR might be advantageous over SPACE-STIR for high-resolution and isotropic head and neck imaging. Only for materials with high-susceptibility differences to soft tissue, the use of SEMAC-STIR might be beneficial. Within limited acquisition times, SEMAC-STIR cannot exploit its full advantage over TSE-STIR regarding artifact suppression.

The Quest for more Research on Painful Diabetic Neuropathy.

A 62-year-old diabetologist diagnosed himself to have diabetes type-2, with an HbA1c of 9.5. Five months after lifestyle intervention and a multi-drug approach, HbA1c was 6.3, systolic blood pressure was below 135mmHg and BMI reduced to 27. But he suffered from severe painful diabetic neuropathy. Therefore he decided to visit his friend, a famous neuroscientist at an even more famous university. He asked him several plain questions: 1. What is the natural course of painful diabetic neuropathy? 2. Why do I have, despite almost normalizing HbA1c, more problems than before? 3. Are you sure my problems are due to diabetes or should we do a nerve biopsy? 4. Are there imaging techniques helpful for the diagnosis of this diabetic complication, starting in the distal nerve endings of the foot and slowly moving ahead? 5. Can you suggest any drug, specific and effective, for relieving painful diabetic neuropathy? This review will use the experts' answers to the questions of the diabetologist, not only to give a summary of the current knowledge, but even more to highlight areas of research needed for improving the fate of patients with painful diabetic neuropathy. Based on the unknowns, which exceed the knowns in diabetic neuropathy, a quest for more public support of research is made.

The human topoisomerase I gene promoter is regulated by NF-IL6.

We investigated the expression of the human DNA topoisomerase I (hTOP1) gene in HeLa cells and in adenovirus-transformed 293 cells. A highly conserved proximal promoter element is essential for hTOP1 promoter activity in HeLa cells but not in 293 cells. This correlates with the presence of specific promoter-binding proteins in HeLa cells and their absence in 293 cells. We identified the HeLa binding protein by screening a cDNA expression library with the specific promoter site as a probe and demonstrate now that the activating protein is identical to the nuclear factor for interleukin-6 expression (NF-IL6), a member of the C/EBP family of transcription factors. Overexpression of NF-IL6 strongly stimulates hTOP1 promoter activity in HeLa cells, suggesting that NF-IL6 is a major hTOP1-regulating protein. Because of the presence of adenovirus protein E1A, 293 cells express the hTOP1 gene more efficiently than HeLa cells but do not contain NF-IL6 activity. E1A activation of the hTOP1 promoter is suppressed by NF-IL6 overexpression. This result supports previous observations concerning a functional interaction between viral protein E1A and NF-IL6. Finally, we show that hTOP1 gene expression in differentiating macrophages is correlated with the synthesis of NF-IL6-specific mRNA.

Application of a Dedicated Surface Coil in Dental MRI Provides Superior Image Quality in Comparison with a Standard Coil.

PURPOSE: Purpose of our research was the evaluation of a dedicated dental surface coil in comparison with a standard head and neck coil for the improvement of dental magnetic resonance imaging (MRI). MATERIALS AND METHODS: Axial T1-weighted spin echo MRI was performed by using a newly developed dental coil for MRI and a standard head and neck coil on five volunteers. In addition, MRI was implemented with dental coil on five patients. Using the Wilcoxon test, we compared the volunteers' signal-to-noise ratio (SNR) of a variety of anatomical structures (e.g., hard tooth tissue, pulp tissue, bone, muscle tissue). Also subjective evaluation of image quality was performed on both volunteers and patients. RESULTS: Compared with the head and neck coil, the mean SNR was 3.5-fold higher on an average with the dental coil (range: from 2.7 [masseter muscle] to 4.6 [pulp tissue]). That difference was statistically significant for all evaluated structures. The higher SNR also resulted in a superior image quality as determined by subjective evaluation. CONCLUSION: Dental MRI benefits profoundly from using a dedicated dental coil.

The influence of spatial patterns of capillary networks on transverse relaxation.

Tissue-inherent relaxation parameters offer valuable information about the arrangement of capillaries: in an external field, capillaries act as magnetic perturbers to generate local inhomogeneous fields due to the susceptibility difference of deoxygenated blood and the surrounding tissue. These field inhomogeneities influence the free induction decay in a characteristic way, and, conversely, the above tissue parameters can be recovered by multi-parametric fits of adequate theoretical models to experimentally sampled free induction decays. In this work we study the influence of different spatial patterns of capillary positions on the free induction decay. Starting from the standard single capillary approximation (Krogh cylinder) for a symmetric array of capillaries, the free induction decay is analyzed for increasingly random capillary positions, using a previously described Gibbs point field model. The effects of diffusion are implemented with a flexible and fast random walk simulation. We find that the asymmetric form of the obtained frequency distribution is more robust against variations of capillary radii than against shifts of capillary positions, and further that, for an inclusion of diffusion effects, the single capillary approximation models the uniform alignment of capillaries in the hexagonal lattice to great accuracy. An increase in randomization of capillary positions then leads to a significant change in relaxation times. This effect, however, is found less pronounced than that of changes in the off-resonance field strengths which are controlled by the oxygen extraction fraction, thus indicating that observed changes in BOLD imaging are more likely to be attributed to changes in oxygenation than to capillary alignment.

3.0 Tesla contrast-enhanced MR angiography of carotid artery stents: in vitro measurements as compared with 1.5 Tesla.

BACKGROUND AND PURPOSE: To assess the appearance of carotid artery stents at 3.0 Tesla contrast enhanced magnetic resonance angiography (CE-MRA) as compared with 1.5 Tesla. METHODS: 19 stents (GUIDANT Acculink, GUIDANT Dynalink, BOSTON SCIENTIFIC SMART Neuroform, GUIDANT Omnilink, EV3 Protege, BOSTON SCIENTIFIC Carotid Wallstent, ABBOTT Xact) of different materials (nitinol, stainless steal, cobalt alloy) and different sizes (4.0 mm-10.0 mm) were investigated regarding their appearance on CE-MRA at 3.0 Tesla and at 1.5 Tesla. For each stent artificial lumen narrowing (ALN) was calculated based on a pixel-by-pixel profile of the contrast-to-noise-ratio giving an objective indicator for the size of the evaluable stent diameter. RESULTS: Only in two stents (Omnilink 7.0 mm, Omnilink 10.0 mm) was ALN higher at 3.0 Tesla relative to 1.5 Tesla. In all other stents ALN at 3.0 Tesla was the same or even lower as compared with 1.5 Tesla. In contrast to the ferromagnetic stents where ALN was typically higher than 85%, in most of the nitinol stents (Acculink, Dynalink, Neuroform, Protege) ALN was below 35%. In the Xact stents ALN was generally 100% at 1.5 Tesla and ranged between 31.8% and 100% at 3.0 Tesla. CONCLUSION: CE-MRA after carotid artery stenting is considerably impaired by ALN both at 1.5 Tesla and at 3.0 Tesla. Nevertheless, CE-MRA is well suited for the examination of carotid artery stents made of nitinol at both field strengths. Stent manufacturers should be aware of potential artifacts caused by their stents during noninvasive diagnostic methods such as CE-MRA.

CPMG relaxation rate dispersion in dipole fields around capillaries.

Transverse relaxation rates for Carr-Purcell-Meiboom-Gill (CPMG) sequences increase with inter-echo time in presence of microscopic magnetic field inhomogeneities due to nuclear spin diffusion. For a weak field approximation that includes diffusion effects, the CPMG relaxation rate shift for proton diffusion around capillaries in muscle tissue can be expressed in terms of a frequency correlation function and the inter-echo time. The present work provides an analytical expression for the local relaxation rate shift that is dependent on local blood volume fraction, diffusion coefficient, capillary radius, susceptibility difference and inter-echo time. Asymptotic regions of the model are in agreement with previous modeling results of Brooks et al., Luz et al. and Ziener et al. In comparison with simulation data, the model shows an equal or better accuracy than established approximations. Also, model behavior coincides with experimental data for rat heart and skeletal muscle. The present work provides analytical tools to extract sub-voxel information about uniform capillary networks that can be used to study capillary organization or micro-circulatory remodeling.

Spin dephasing in a magnetic dipole field around large capillaries: Approximative and exact results.

We present an analytical solution of the Bloch-Torrey equation for local spin dephasing in the magnetic dipole field around a capillary and for ensembles of capillaries, and adapt this solution for the study of spin dephasing around large capillaries. In addition, we provide a rigorous mathematical derivation of the slow diffusion approximation for the spin-bearing particles that is used in this regime. We further show that, in analogy to the local magnetization, the transverse magnetization of one MR imaging voxel in the regime of static dephasing (where diffusion effects are not considered) is merely the first term of a series expansion that constitutes the signal in the slow diffusion approximation. Theoretical results are in agreement with experimental data for capillaries in rat muscle at 7T.

Conserved regulatory elements in the type I DNA topoisomerase gene promoters of mouse and man.

The gene for mammalian type I DNA topoisomerase is constitutively expressed, but also regulated by a number of external stimuli. We compared the nucleotide sequences of the human and the mouse topoisomerase I gene promoters because promoter elements, essential for basic as well as regulated gene expression, should be conserved during evolution. We found that proximal upstream sequences are highly conserved and include potential binding sites for ubiquitous transcription factors, a regulatory CRE site as well as two novel promoter elements that have been shown to be important for the expression of the human gene. The more distal parts of the upstream sequences are less well conserved but include two regions that are almost identical in the human and the mouse gene. One of these regions contains a binding site for a basic-helix-loop-helix/leucine-zipper protein, and the other contains an AT-rich element with the potential for DNA bending.

[Pseudonormalization of diffusion weighted images: magnetic resonance imaging in an animal model (C6-glioma)]. / Pseudonormalisierung diffusionsgewichteter Aufnahmen: Magnetresonanztomografische Untersuchungen im Tiermodell (C6-Gliom).

PURPOSE: Previous studies on intracranial tumors indicate that a high apparent diffusion coefficient (ADC) is due to low cellularity and that lower values indicate a dense, highly cellular tumor. Diffusion is affected by three major factors: cell density, existence and distribution of vasogenic edema, and hypoxic tissue. Therefore, we studied the characteristics of diffusion-weighted magnetic resonance imaging (DWI) in a rat brain C6 glioma during tumor progression. MATERIALS AND METHODS: In male Wistar rats, C6 gliomas were implanted in the caudoputamen. At day 9, 11, 13 and 15 after tumor inoculation, conventional DWI was performed on a 2.35 Tesla small bore MRI unit (Biospec 24/40, BRUKER Medizintechnik, Ettlingen, Germany). RESULTS: On conventional T2-weighted and contrast-enhanced T1-weighted images, all tumors could well be delineated from the surrounding brain tissue and showed significant progression. On DWI, the tumors were isointense or slightly hypointense compared to the surrounding brain. On the ADC maps, the tumors could be well visualized due to increasing ADC values from day 9 to 15. The mean ADC of brain tumor tissue was 0.76 +/- 0.4 x 10 ( - 3) mm (2)/s at day 9 and 0.91 +/- 0.03 x 10 ( - 3) mm (2)/s at day 15. The mean ADC of the normal contralateral caudoputamen was 0.59 +/- 0.007 x 10 ( - 3)mm (2)/s. CONCLUSION: T2 prolongation and increased water diffusion can be balanced on DWI in C6 gliomas, resulting in isointensity on DWI (T2 shine-through washout phenomenon). ADC maps are indispensable for the correct interpretation of tumor tissue diffusion behavior.