Measuring Brain Tissue Integrity during 4 Years Using Diffusion Tensor Imaging.

BACKGROUND AND PURPOSE: DTI is an MR imaging measure of brain tissue integrity. Little is known regarding the long-term longitudinal evolution of lesional and nonlesional tissue DTI parameters in multiple sclerosis and the present study examines DTI evolution over 4 years. MATERIALS AND METHODS: Twenty-one patients with multiple sclerosis were imaged for up to 48 months after starting natalizumab therapy. Gadolinium-enhancing lesions at baseline, chronic T2 lesions, and normal-appearing white matter were followed longitudinally. T2 lesions were subclassified as black holes and non-black holes. Within each ROI, the average values of DTI metrics were derived by using Analysis of Functional Neuro Images software. The longitudinal trend in DTI metrics was estimated by using a mixed-model regression analysis. RESULTS: A significant increase was observed for axial diffusivity (P < .001) in gadolinium-enhancing lesions and chronic T2 lesions during 4 years. No significant change in radial diffusivity either in normal-appearing white matter or lesional tissue was observed. The evolution of axial diffusivity was different in gadolinium-enhancing lesions (P < .001) and chronic T2 lesions (P = .02) compared with normal-appearing white matter. CONCLUSIONS: An increase in axial diffusion in both gadolinium-enhancing lesions and T2 lesions may relate to the complex evolution of chronically demyelinated brain tissue. Pathologic changes in normal-appearing white matter are likely more subtle than in lesional tissue and may explain the stability of these measures with DTI.

Sex differences in resting-state functional connectivity in multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple studies have demonstrated evidence of sex differences in patients with MS, including differences in disease progression, cognitive decline, and biologic markers. This study used functional connectivity MRI to investigate sex differences in the strength of functional connectivity of the default mode network in patients with MS and healthy control subjects. MATERIALS AND METHODS: A total of 16 men and 16 women with MS and 32 age- and sex-matched healthy control subjects underwent a whole-brain resting-state functional connectivity MRI scan. A group-based seed in the posterior cingulate was used to create whole-brain correlation maps. A 2 × 2 ANOVA was used to assess whether disease status and sex affected the strength of connectivity to the posterior cingulate. RESULTS: Patients with MS showed significantly stronger connectivity from the posterior cingulate to the bilateral medial frontal gyri, the left ventral anterior cingulate, the right putamen, and the left middle temporal gyrus (P < .0005). In the left dorsal lateral prefrontal cortex, female patients showed significantly stronger connectivity to the posterior cingulate cortex compared with female control subjects (P = 3 × 10(4)), and male control subjects showed stronger posterior cingulate cortex-left dorsal lateral prefrontal cortex connectivity in comparison to female control subjects (P = .002). Male patients showed significantly weaker connectivity to the caudate compared with female patients (P = .004). CONCLUSIONS: Disease status and sex interact to produce differences in the strength of functional connectivity from the posterior cingulate to the caudate and the left dorsal lateral prefrontal cortex.

Sensorimotor cortex gamma-aminobutyric acid concentration correlates with impaired performance in patients with MS.

BACKGROUND AND PURPOSE: Abnormalities in GABA concentration [GABA] have been associated with several neuropsychiatric disorders, and research has suggested that GABA may play a role in sensorimotor cortex function. We sought to determine whether identifying a change in [GABA] within the sensorimotor cortex of patients with MS has any effect on motor function and would provide information about the adaptive/compensatory mechanisms involved in the attempt to maintain motor function during disease progression. MATERIALS AND METHODS: In 19 healthy controls and 30 patients with MS, we assessed task performance with the MS Functional Composite scale and its components (T25FW test, 9HPT, and PASAT). With in vivo MR spectroscopy, we measured [GABA] in the sensorimotor cortex and determined correlations between [GABA] and task performance. We also assessed the association between [GABA] and cortical activation volume after a bilateral finger-tapping task. RESULTS: [GABA] was inversely correlated with 9HPT scores in patients with MS, indicating a worsening of performance with increased [GABA]. No significant correlation was observed between [GABA] and T25FW or PASAT scores. [GABA] was directly correlated with primary motor cortex activation volume after the finger-tapping task in patients with MS. CONCLUSIONS: These results suggest that cortical [GABA] may be a marker of function and reorganization/adaptation of cortical gray matter in MS.

Application of a computerized language lateralization index from FMRI by a group of clinical neuroradiologists.

BACKGROUND AND PURPOSE: Deriving accurate language lateralization from fMRI studies in the clinical context can be difficult, with 10%-20% incorrect conclusions. Most interpretations are qualitative, performed by neuroimaging experts. Quantitative lateralization has been widely described but with little implementation in the clinical setting and is disadvantaged by the use of arbitrary threshold techniques. We investigated the application and utility of a nonthreshold CLI, in a clinical setting, as applied by a group of practicing neuroradiologists. MATERIALS AND METHODS: Twenty-two patients with known language lateralization (11 left and 11 nonleft dominant) had their images reviewed by 8 neuroradiologists in 2 settings, all randomized, once by using a CLI and once without using a CLI. For each review, neuroradiologists recorded their impressions of lateralization for each language sequence, the overall lateralization conclusion, their impression of scan quality and noise, and the subjective confidence in their conclusion. RESULTS: The inter-rater κ for lateralization was 0.64, which increased to 0.70 with the use of CLI. The group accuracy of overall lateralization was 78%, which increased to 81% with the use of a CLI. Using a CLI removed 2 instances of significant errors, with a neuroradiologist's impression of left lateralization in a patient with known right lateralization. Using a CLI had no effect on examinations with conclusions formed with either high confidence or no confidence. CONCLUSIONS: Although the overall clinical benefit of a CLI is modest, the most significant impact is to reduce the most harmful misclassification errors, particularly in fMRI examinations that are suboptimal.

Measuring myelin repair and axonal loss with diffusion tensor imaging.

BACKGROUND AND PURPOSE: DTI is an MR imaging measure of brain tissue integrity and provides an attractive metric for use in neuroprotection clinical trials. The purpose of our study was to use DTI to evaluate the longitudinal changes in brain tissue integrity in a group of patients with MS. MATERIALS AND METHODS: Twenty-one patients with MS starting natalizumab were imaged serially for 12 months. Gadolinium-enhancing lesions and 20 regions of interest from normal-appearing white and gray matter brain tissue were followed longitudinally. Average values within each region of interest were derived for FA, λ(∥), λ(⊥), and MD. New T1 black holes were identified at 12 months. Analysis was performed by using mixed-model regression analysis with slope (ie, DTI change per month) as the dependent variable. RESULTS: During 1 year, FA increased in gadolinium-enhancing lesions but decreased in NABT (P < .0001 for both). Changes in FA within gadolinium-enhancing lesions were driven by decreased λ(⊥) (P < .001), and within NABT, by decreased λ(∥) (P < .0001). A higher λ(⊥) within gadolinium-enhancing lesions at baseline predicted conversion to T1 black holes at 12 months. MD was unchanged in both gadolinium-enhancing lesions and NABT. CONCLUSIONS: We observed changes in DTI measures during 1 year in both gadolinium-enhancing lesions and NABT. The DTI results may represent possible remyelination within acute lesions and chronic axonal degeneration in NAWM. These results support the use of DTI as a measure of tissue integrity for studies of neuroprotective therapies.

Effect of a prescan patient-radiologist encounter on functional MR image quality.

BACKGROUND AND PURPOSE: A substantial number of clinical fMRI examinations inadequately assess language localization or lateralization, usually due to patient movement and suboptimal participation. We hypothesized that a prescan interview of the patient by the radiologist would reduce the fraction of nondiagnostic scans. MATERIALS AND METHODS: A single noise score for each acquisition was produced from time-series data on the basis of a weighted sum of 22 factors. Scores were recorded as the following quartiles: 0-5 = excellent, 5-10 = adequate, 10-15= marginal, and >15 = unacceptable. This measure was evaluated for 202 consecutive fMRI patients: 96 without and 106 with a physician prescan interview. The data were analyzed to compute the fraction of all nondiagnostic sequences and entire studies and were compared between the 2 groups. Image-noise characteristics included the SDs of linear and angular displacements of the head and the number of time-series outliers caused by focal motion. RESULTS: Of 999 sequences acquired, 539 had a prescan interview. The mean noise score significantly decreased for both individual sequence (from 7.9 to 6.3, P = <.001) and study-based (from 7.7 to 6.2, P = .05) methods. The fraction of sequences or studies scored as unacceptable decreased for sequence-based (from 15.2% to 10.9%, P = .04) and study-based (from 9.4% to 1.9%, P = .02) analyses. SDs of head motion decreased for linear (by 12%-14%, P < .01) and angular displacement (by 38%-48%, P < .001). The number of time-series spikes decreased by 10% (P = .004). CONCLUSIONS: We report that a prescan physician-patient interview modestly but significantly reduces fMRI noise scores. These results support the newly added billable costs of professional intervention before fMRI scans.

Resistance exercise and lipoproteins in postmenopausal women.

The specific aims of this study were to quantify the effects of 12 weeks of resistance training, as well as a single session of resistance exercise on lipids and lipoproteins in obese, postmenopausal women. 21 obese, postmenopausal women, not on hormone replacement therapy (age=65.9 ± 0.5 yr; BMI=32.7 ± 0.8 kg/m(2)), were randomly assigned to control (n=12) and exercise (n=9) groups matched for age and BMI. For 12 weeks, 3 days/week, the exercise group performed 10 whole body resistance exercises (3 sets at 8-RM). Fasting (10 h) blood samples were collected immediately prior to and 24 h after the first and last exercise and control session. Serum was assayed for concentrations of total cholesterol, triglycerides, LDL-C, HDL-C, HDL 2-C, HDL 3-C, non-HDL-C and TC:HDL and LDL:HDL ratios. The exercise group exhibited a significant (P<0.01) improvement in muscular strength, but no change in BMI, body mass or body composition post-training. Total cholesterol, LDL-C and non-HDL-C were significantly (P<0.05) lower in the exercise compared to the control group following the 12 weeks of resistance training. Whole body resistance training provides obese, postmenopausal women a non-pharmacological approach for the reduction of lipid and lipoprotein-cholesterol concentrations.

Resistive exercise blunts LPS-stimulated TNF-alpha and Il-1 beta.

To examine the influence of acute resistive exercise and "hormone status" on cytokine profile, 35 postmenopausal women (72 +/- 6.2 yr) underwent a moderate-high-intensity resistive exercise bout or rested. There were 4 groups: no hormone replacement (NHR, n = 9), hormone replacement (HRT, n = 12), selective estrogen receptor modulator (SER, n = 7), or resting control (no hormone replacement, CON, n = 7). NHR, HRT, and SER exercised (3 sets, 10 exercises @ 80 % 1RM). Blood was collected pre-exercise (PR), postexercise (PO), and two hours (2H) postexercise (same times for CON). Blood was diluted 1 : 10 in culture medium and incubated (37 degrees C, 5 % CO2, 24 h) with lipopolysaccharide (LPS, 25 microg . ml (-1)). Serum and supernatant from LPS-stimulated blood were analyzed for IL-6, IL-1 beta, and TNF-alpha using ELISA. Resistive exercise increased PO serum IL-6, and PO LPS-stimulated IL-6 and IL-1 beta in the exercise groups (HRT, NHR, SER collapsed; EX, n = 28). LPS-stimulated IL-1 beta remained elevated at 2H in EX and was significantly higher than PR in CON at 2H. Expressed per monocyte, EX had significantly lower IL-1 beta and TNF-alpha LPS-stimulated production at PO and 2H compared to CON, indicating an exercise-induced blunting of an apparent diurnal response on cytokine production. In postmenopausal women, acute resistive exercise increased circulating IL-6, but reversed an apparent diurnal increase in LPS-stimulated IL-1 beta and TNF-alpha production with no influence of hormone replacement or raloxifene.

Spectral quality control in motion-corrupted single-voxel J-difference editing scans: an interleaved navigator approach.

Motion has an adverse effect on spectral quality and needs to be properly identified in MR spectroscopy (MRS) scans. Spectral subtraction-based techniques like J-difference editing are prone to be affected more by subject motion where motion can result in false peaks or inefficient subtraction of peaks. Introducing a water signal-based interleaved navigator scan in the MEGA point-resolved spectroscopy (MEGA-PRESS) sequence and acquiring data on a shot-by-shot basis, subject motion inside a scanner was tracked and motion-corrupted data were identified and excluded from the dataset. Performing a gamma-aminobutyric acid (GABA) editing scan at the occipital cortex, it was possible to retrieve a properly edited GABA spectrum from a dataset otherwise to be discarded due to motion. This study demonstrates the importance of independent motion assessment in J-difference editing.

Hydrogen bonding and multiphonon structure in copper pyrazine coordination polymers.

We report a systematic investigation of the temperature-dependent infrared vibrational spectra of a family of chemically related coordination polymer magnets based upon bridging bifluoride (HF(2)-) and terminal fluoride (F-) ligands in copper pyrazine complexes including Cu(HF(2))(pyz)(2)BF(4), Cu(HF(2))(pyz)(2)ClO(4), and CuF(2)(H(2)O)(2)(pyz). We compare our results with several one- and two-dimensional prototype materials including Cu(pyz)(NO(3))(2) and Cu(pyz)(2)(ClO(4))(2). Unusual low-temperature hydrogen bonding, local structural transitions associated with stronger low-temperature hydrogen bonding, and striking multiphonon effects that derive from coupling of an infrared-active fundamental with strong Raman-active modes of the pyrazine building-block molecule are observed. On the basis of the spectroscopic evidence, these interactions are ubiquitous to this family of coordination polymers and may work to stabilize long-range magnetic ordering at low temperature. Similar interactions are likely to be present in other molecule-based magnets.

Magnetothermal transport in the spin-1/2 chains of copper pyrazine dinitrate.

We present experiments on the thermal transport in the spin-1/2 chain compound copper pyrazine dinitrate Cu(C4H4N2)(NO3)2. The heat conductivity shows a surprisingly strong dependence on the applied magnetic field B, characterized at low temperatures by two main features. The first one appearing at low B is a characteristic dip located at muBB approximately kBT, that may arise from umklapp scattering. The second one is a plateaulike feature in the quantum critical regime, muB|B - Bc| < kBT, where Bc is the saturation field at T=0. The latter feature clearly points towards a momentum and field-independent mean free path of the spin excitations, contrary to theoretical expectations.

Diffusion-weighted imaging of white matter abnormalities in patients with phenylketonuria.

Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of the enzyme phenylalanine hydroxylase (EC 1.14.16.1). Affected patients develop elevated plasma and tissue levels of phenylalanine and its related ketoacids. Untreated patients usually exhibit severe mental retardation and poor motor function, with characteristic T2 white matter signal abnormalities on conventional MR images. In the present study, we performed diffusion-weighted imaging in three PKU patients. All three patients demonstrated significantly restricted diffusion in all white matter areas examined.

Approach to functional magnetic resonance imaging of language based on models of language organization.

Functional MR imaging (fMRI) has been a useful tool in the evaluation of language both in normal individuals and patient populations. The purpose of this article is to use various models of language as a framework to review fMRI studies. Specifically, fMRI language studies are subdivided into the following categories: word generation or fluency, passive listening, orthography, phonology, semantics, and syntax.

Temporal lobe activation demonstrates sex-based differences during passive listening.

PURPOSE: To evaluate potential sex differences in temporal lobe activation during the performance of a functional magnetic resonance (MR) imaging passive-listening paradigm. MATERIALS AND METHODS: Twenty strongly right-handed volunteers (10 men, 10 women) underwent imaging with a 1.5-T machine by using a gradient-echo echo-planar sequence. The task consisted of passive listening to simple narrative text interleaved with same-narrative text played backward. Volumes of interest were drawn around anterior and posterior areas of activation in bilateral temporal lobes. The peak percentage of activation and the percentage of activated voxels at single-voxel significance levels of 10(-2), 10(-3), and 10(-4) within each volume of interest were measured. An asymmetry index A was then calculated for both anterior and posterior volumes of interest such that A = (L - R)/(L + R), where R is either the peak percentage activation or the percentage of activated voxels within the right volume of interest and L is either the peak percentage activation or the percentage of activated voxels within the left volume of interest. The asymmetry indexes were compared between men and women by using a standard t test. RESULTS: Men showed a significantly higher degree of asymmetric activation than did women in both the anterior and posterior volumes of interest by using peak percentage activation and at all single-voxel significance levels. The degree of activation asymmetry was greater by using single-voxel significance measurements, compared with peak percentage activation measures. CONCLUSION: Women demonstrate a higher degree of bilateral language representation in temporal lobe regions than do men during passive listening. These findings, combined with the variable results of prior functional MR imaging language studies of sex differences, suggest that they may be task specific.

Adherence to care plan in women with abnormal Papanicolaou smears: a review of barriers and interventions.

BACKGROUND: Cancer of the cervix is preventable. According to the Surveillance, Epidemiology, and End Results (SEER) Program, invasive cervical cancer incidence is 9.0 and cancer mortality rate is 2.8 per 100,000 persons. Effective prevention includes appropriate use of Papanicolaou smears and adherence to a care plan by the patient. This review will examine the extent of nonadherence, negative outcomes, barriers, and interventions for improved adherence to care. METHODS: Computer searches in MEDLINE for English language articles were conducted from 1968 to 1999 using the key words "colposcopy," "abnormal Papanicolaou smear," "patient compliance," "adherence to care," and "follow-up." RESULTS: Although there is 10% to 40% nonadherence in the studies reviewed, the definition of nonadherence is not standard. Considerable morbidity from cervical cancer was described among nonadherent women. The most common barriers to follow-up were lack of understanding of the purpose of colposcopy, fear of cancer, forgetting appointments, and lack of time, money, or childcare. Emotional consequences of abnormal Papanicolaou smears had considerable impact on follow-up visits. Focused intervention strategies targeted to the study population were most effective in improving adherence. CONCLUSIONS: Nonadherence results from the interplay of emotional, logistic, cultural, or socioeconomic factors. Among the most effective strategies to improve adherence are personalized reminders to patients by their primary physicians and case management dictated by the size, structure, and style of the practice.

Improving clinical histories on radiology requisitions.

PURPOSE: The Health Care Financing Administration (HCFA) regards billing for radiologic examinations without an appropriate indication as unlawful, and both the referring physician and the radiologist are liable. HCFA regulations are interpreted as requiring that all requisitions for radiologic examinations include a current diagnosis and appropriate indication for the study. The purpose of this investigation was to determine the rates at which requisitions currently meet these criteria and to assess the effectiveness of a simple intervention designed to improve them. MATERIALS AND METHODS: One hundred fifty consecutive chest radiography requisitions were examined to determine the rate at which current diagnoses and appropriate indications were present. An intervention was then implemented that included a month-long effort to inform referring physicians and radiologists of HCFA regulations, followed by a 1-week period during which requested examinations were not performed unless accompanied by a clinical diagnosis and appropriate indication. Another 150 consecutive chest radiography requisitions were then assessed to determine the effect of the intervention. A 3-month follow-up sample of a third set of 150 consecutive requisitions was then obtained. RESULTS: The intervention produced a 69% decrease in the rate at which current diagnoses were missing from requisitions, and a 61% decrease in the corresponding rate for appropriate indications. Both results are significant with chi2 analysis at the P = .001 level. After 3 months with no additional intervention, rates decayed back toward baseline, with only a 35% remaining decrease for current diagnosis and an 18% decrease for appropriate indication. CONCLUSION: The intervention performed in this study significantly reduces the rate of noncompliance with HCFA regulations. However, this improvement decays over time if it is not reinforced.

Characterization of a novel autosomal dominant bleeding disorder in a large kindred from east Texas.

A large east Texas family with autosomal dominant inheritance of a novel bleeding disorder has been identified. The disorder is characterized clinically by easy bruising, life-threatening bleeding with trauma or surgery, and menorrhagia in affected women. Laboratory studies demonstrated prolongation of the prothrombin time and activated partial thromboplastin time in affected individuals. Paradoxically, assays of known coagulation factors are all within normal limits. To determine the molecular basis of this disease, a candidate gene linkage analysis in this kindred was done. Initially it was hypothesized that the cause of the disease in this family could be an antithrombin III (AT3) mutation that resulted in a constitutively active AT3 in the absence of heparin binding. Linkage studies using DNA from the family and an intragenic polymorphic marker within the AT3 gene showed that the disease mapped to this locus. The coding region and intron/exon junctions of AT3 were sequenced using the proband's DNA, but this analysis failed to identify a mutation. Additional family members were recruited for the study, and 16 polymorphic markers around the AT3 gene were analyzed. Using 2 recombinants, the critical interval for the defective gene was narrowed to approximately 1.5 Mb, centromeric to AT3. The factor V (FV) gene was mapped into the disease interval and sequenced; there were no mutations found. Elucidation of the genetic defect causing the bleeding disorder in this family may reveal a novel protein involved in the coagulation cascade.

Multisection CT: scanning techniques and clinical applications.

Multisection computed tomography (CT) was introduced in 1992 with the advent of dual-section-capable scanners and was improved in 1998 following the development of quad-section technology. With a recent increase in gantry speed from one to two revolutions per second, multisection CT scanners are now up to eight times faster than conventional single-section helical CT scanners. The benefits of quad-section CT relative to single-section helical CT are considerable. They include improved temporal resolution, improved spatial resolution in the z axis, increased concentration of intravascular contrast material, decreased image noise, efficient x-ray tube use, and longer anatomic coverage. These factors substantially increase the diagnostic accuracy of the examination. The multisection CT technique has enabled faster and superior evaluation of patients across a wide spectrum of clinical indications. These include isotropic viewing, musculoskeletal applications, use of multiplanar reformation in special situations, CT myelography, long coverage and multiphase studies, CT angiography, cardiac scoring, evaluation of brain perfusion, imaging of large patients, evaluation of acute chest pain or dyspnea, virtual endoscopy, and thin-section scanning with retrospective image fusing. Multisection CT is superior to single-section helical CT for nearly all clinical applications.

Correlations in low-frequency BOLD fluctuations reflect cortico-cortical connections.

Cross-correlation of low-frequency temporal fluctuations (<0.08 Hz) was used to correlate widely separated anatomic regions during continuous performance of a spatial working memory task. The regions of highest correlation to right-hemisphere dorsolateral prefrontal cortex correspond to the regions of largest baseline signal change in a conventional block-style functional MRI paradigm. Additionally, it is shown that the correlations between elements of the functional network increase during performance of a task that activates the network when compared to a task that does not directly stimulate the functionally connected network.