Functional deficits in basal ganglia of children with attention-deficit/hyperactivity disorder shown with functional magnetic resonance imaging relaxometry.

Attention-deficit/hyperactivity disorder is a highly heritable and prevalent neuropsychiatric disorder estimated to affect 6% of school-age children. Its clinical hallmarks are inattention, hyperactivity and impulsivity, which often respond substantially to treatment with methylphenidate or dextroamphetamine. Etiological theories suggest a deficit in corticostriatal circuits, particularly those components modulated by dopamine. We developed a new functional magnetic resonance imaging procedure (T2 relaxometry) to indirectly assess blood volume in the striatum (caudate and putamen) of boys 6-12 years of age in steady-state conditions. Boys with attention-deficit/hyperactivity disorder had higher T2 relaxation time measures in the putamen bilaterally than healthy control subjects. Relaxation times strongly correlated with the child's capacity to sit still and his accuracy in accomplishing a computerized attention task. Daily treatment with methylphenidate significantly changed the T2 relaxation times in the putamen of children with attention-deficit/hyperactivity disorder, although the magnitude and direction of the effect was strongly dependent on the child's unmedicated activity state. There was a similar but nonsignificant trend in the right caudate. T2 relaxation time measures in thalamus did not differ significantly between groups, and were not affected by methylphenidate. Attention-deficit/hyperactivity disorder symptoms may be closely tied to functional abnormalities in the putamen, which is mainly involved in the regulation of motor behavior.

Cocaine-induced cerebral vasoconstriction differs as a function of sex and menstrual cycle phase.

BACKGROUND: Chronic cocaine abusing women experience fewer cerebral perfusion defects and less neuronal injury than men with comparable drug use histories. This study assessed whether a basis for this discrepancy is a sex difference in cocaine's acute cerebrovascular effects. METHODS: The subjects in this study were 13 healthy and neurologically normal women, reporting occasional cocaine (mean 13, range 1-40 lifetime cocaine exposures). All subjects were administered cocaine (0.4 mg/kg) intravenously, during both the follicular (days 3-8) and luteal (days 18-24) menstrual cycle phases. Dynamic susceptibility contrast magnetic resonance imaging assessments of relative global cerebral blood volume (CBV) changes were conducted on both study days, 10 min after cocaine administration. RESULTS: Cocaine did not alter CBV in follicular phase women, but reduced luteal phase CBV by 10%, indicative of vasoconstriction (analysis of variance [ANOVA], F = 5.1, p <.05). Postcocaine CBV was lower in men administered the drug via an identical protocol relative to follicular phase women (ANOVA, F = 5.4, p <.04). Postcocaine CBV was also lower in the male referent group relative to luteal phase women, but this difference did not achieve statistical significance. No measurable sex or menstrual cycle phase differences in cocaine's cardiovascular effects were noted. CONCLUSIONS: These findings suggest both menstrual cycle phase and sex differences in cocaine's acute cerebrovascular effects, which may contribute to sex differences in the severity of brain dysfunction found in chronic cocaine abusers. These findings imply that gonadal steroids or the factors they modulate merit study as possible therapeutic agents for reducing cocaine-induced cerebrovascular disorders.

Functional magnetic resonance imaging of human brain activation during cue-induced cocaine craving.

OBJECTIVE: Functional magnetic resonance imaging (MRI) was used to test whether brain activation was detectable in regions previously associated with cocaine cue-induced craving. METHOD: Blood oxygenation level dependent (BOLD) functional activation was measured during presentation of audiovisual stimuli containing alternating intervals of drug-related and neutral scenes to six male subjects with a history of crack cocaine use and six male comparison subjects. RESULTS: Significant activation was detected in the anterior cingulate and left dorsolateral prefrontal cortex in the cocaine-using group. In addition, a correlation between self-reported levels of craving and activation in these regions was found. CONCLUSIONS: These results suggest that functional MRI may be a useful tool to study the neurobiological basis of cue-induced craving.

Age-related reduction in functional MRI response to photic stimulation.

Many functional imaging studies have demonstrated age-related alterations in cerebral blood flow during the resting state. However, few studies have addressed possible differences in functional response to cerebral activation. We assessed the response of visual cortex to photic stimulation in 9 normal elderly subjects and 17 normal younger subjects with blood oxygenation level dependent functional magnetic resonance imaging. We found that the amplitude of response in elderly subjects was significantly decreased compared to younger subjects (2.5 +/- 1.0% versus 4.0 +/- 1.6%, p = 0.01), suggesting a reduction in functional activation or an age-related alteration in the coupling of blood oxygenation to focal activation.

Cocaine decreases relative cerebral blood volume in humans: a dynamic susceptibility contrast magnetic resonance imaging study.

Cocaine has substantial effects on cerebral hemodynamics which may partly underlie both its euphorigenic and toxic effects. Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) was used to determine whether a dose-effect relationship could be detected between cocaine administration and cerebral blood volume reduction in human brain. Twenty-three healthy and neurologically normal adult males with a history of recreational cocaine use (3-40 lifetime exposures) participated. Subjects underwent DSC-MRI measurements of relative cerebral blood volume (rCBV) at baseline and 10 min after i.v. double-blind placebo or cocaine (0.2 or 0.4 mg/kg) administration. Placebo administration resulted in superimposable rCBV curves with post-placebo CBV averaging 104+/-4% (mean+/-SE) of baseline, indicating no CBV change. Both cocaine doses induced CBV decreases which were statistically equivalent and post-cocaine CBV averaged 77+/-4% of baseline (P < 0.002), when measured 10 min following drug administration. These data suggest that DSC-MRI can detect cocaine-induced CBV reductions indicative of vasoconstriction, and that it may be useful for evaluating treatments designed to reduce the cerebrovascular effects of cocaine.

Functional magnetic resonance imaging of facial affect recognition in children and adolescents.

OBJECTIVE: To examine further the role of the amygdala in the recognition of facial expression in adolescents. METHOD: Twelve healthy adolescents were studied using functional magnetic resonance imaging technology during a task of facial affect recognition and a visual control task. RESULTS: All subjects demonstrated a significant increase in signal intensity in the amygdala for the facial expression recognition task. CONCLUSIONS: The data are consistent with previous work in healthy adult subjects implicating the amygdala as essential for the recognition of fearful facial expression.

T1 effects in sequential dynamic susceptibility contrast experiments.

Residual effects of an initial bolus of gadolinium contrast agent have been previously demonstrated in sequential dynamic susceptibility contrast MR experiments. While these residual effects quickly reach a saturation steady state, their etiology is uncertain, and they can lead to spurious estimates of hemodynamic parameters in activation experiments. The possible influence of T1 effects is now investigated with experiments in which T1 weighting is varied as well as with serial regional T1 measurements. Little evidence for significant residual T1 effects is found, suggesting instead that susceptibility effects underlie these observations. An initial saturation dose of contrast agent minimizes this effect.

Myocardial tissue characterization by autocorrelation of two-dimensional ultrasonic backscatter.

To evaluate a novel method for determining the spatial distribution of echocardiographic information based on the two-dimensional autocorrelation function, echocardiographic images were obtained from specific regions of interest from 10 healthy volunteers, seven patients with genetically defined hypertrophic cardiomyopathy, and nine patients with pressure-overload hypertrophy. The wavelength of distinct peaks from the two-dimensional autocorrelation of the images was compared between groups of patients and demonstrated a significant decrease in the mean length scale associated with distinct secondary correlation peaks in patients with hypertrophic cardiomyopathy or pressure-overload hypertrophy compared with healthy volunteers (p = 0.0009). With a discriminating wavelength of 3.3 mm, the sensitivity of this technique for detecting abnormal myocardium was 84% with a specificity of 89%. This study suggests that ultrasonic tissue characterization based on the two-dimensional autocorrelation function may have potential for distinguishing normal from abnormal myocardium and provides a rationale for textural approaches to ultrasonic tissue characterization.

Sex differences in response to red and blue light in human primary visual cortex: a bold fMRI study.

Studies using a variety of investigative methods, including functional brain imaging and electroencephalography (EEG), have suggested that changes in central nervous system (CNS) dopamine function result in altered visual system processing. The discovery of abnormal retinal blue cone, but not red cone, electroretinogram in association with cocaine withdrawal and Parkinson's disease suggests that visual system response to blue light might be a marker for CNS dopamine tone. As there are numerous sex-related differences in central nervous system dopamine function, we predicted that blue and red light stimulation would produce sex-specific patterns of response in primary visual cortex when studied using the blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) technique. We analyzed the BOLD response to red and blue light in male and female human volunteers (N=20). Red and blue light responses in primary visual cortex (V1) to stepped intensities of red and blue light were compared by sex for threshold to detectable BOLD signal increase and for stimulus intensity vs. BOLD signal response. Near threshold, males and females showed similar BOLD signal change to red light, but males showed a threefold greater increase (0.52%) to blue light stimulation when compared to females (0.14%). Log-linear regression modeling revealed that the slope coefficients for the red light stimulus intensity vs. signal change curve were not significantly different for males and females (z=0.995, P=0.320), whereas the slope coefficients for the blue light stimulus intensity vs. signal change curve were significantly larger in males (z=2.251, P=0.024). These findings support a sex and color-dependent differential pattern of primary visual cortical response to photic stimulation and suggest a method for assessing the influence of specific dopamine agonist/antagonist medications on visual function.

Reduction in BOLD fMRI response to primary visual stimulation following alcohol ingestion.

The physiology of alcohol's effects on brain function is poorly understood. Emission tomographic imaging has revealed both acute and chronic alterations in resting cerebral hemodynamics and metabolism following alcohol ingestion. However, cerebral functional integrity under these conditions has received less attention. Functional magnetic resonance imaging (fMRI) offers a non-invasive method for assessing brain functional activation. In order to assess its utility for studying the effect of alcohol on brain function, we performed fMRI with photic stimulation before and after administration of either 0.7 mg/kg alcohol (N = 12) or placebo (N = 5), resulting in peak breath alcohol levels averaging 0.069 g/dl. We found that the amplitude of visual cortical activation in response to photic stimulation was significantly reduced by approximately 33% following alcohol administration (4.0 +/- 1.7% vs. 2.7 +/- 1.3%, P = 0.02), but not following placebo (4.2 +/- 1.5% vs. 4.1 +/- 1.4%, P = 0.7). The results also suggest that the baseline right hemispheric predominance of activation in response to photic stimulation may be reduced following alcohol, suggesting a greater effect on the right hemisphere, consistent with previous studies and alcohol's known effects on visuospatial processing. In addition, through the course of each activation session, there was a progressive reduction in response following alcohol. These data demonstrate that the cerebral effects of alcohol intoxication can be studied with fMRI, and that the effects on brain function of even moderate alcohol intoxication may be widespread, may be lateralized, and may include the visual system.

Functional magnetic resonance imaging of alprazolam-induced changes in humans with familial alcoholism.

This study sought to identify whether subjects with a family history (FH + ) of alcoholism had changes in regional cerebral blood volume (rCBV) after an alprazolam challenge which distinguished them from subjects without a family history (FH -) of alcoholism using functional MRI (fMRI). Twelve FH + and eight FH - subjects were challenged with 1 mg of alprazolam or placebo in a double-blind crossover design. FMRI scans were obtained at baseline, 1 and 2 h after the challenge using the dynamic susceptibility contrast method with gadolinium. Mood scales, the Tufts Addiction Research Center Inventory-Morphine Benzedrine Group Scale and the drug liking scale, were administered every 30 min to assess drug effects. Global analysis of CBV showed a treatment by time decrease on alprazolam relative to placebo, but no effect by family history. The FH + group showed rCBV decreases at 1 h in the left caudate and left inferior prefrontal region, while the FH - group showed rCBV decreases at 2 h in the right inferior prefrontal region and anterior cingulate in response to alprazolam relative to placebo. FH + subjects reported more mood enhancement with alprazolam. This fMRI technique detected global and regional CBV changes induced by alprazolam. The location and rate of alprazolam-induced rCBV changes differed between FH + and FH - subjects. These changes may be related to the increased mood enhancement found in subjects genetically predisposed to alcoholism.

Post-registration spatial filtering to reduce noise in functional MRI data sets.

Image registration is commonly performed in the analysis of functional magnetic resonance imaging data sets. However, the nature of artifacts introduced in the process of alignment has not been well described. In this manuscript, high-frequency losses inherent in image registration are discussed, together with a conceptual division into acquisition- and resampling-related artifacts. Simulated and experimental data are presented to illustrate these artifacts. In simulations comparing corrected and reference images, root mean square (RMS) difference errors of 0.74% and 2.62% were observed following the correction of one degree of rotation for images registered with frequency regridding and bilinear interpolation, respectively. In human experiments, regression of RMS difference error as a percentage of mean brain signal yielded slopes of 0.69 to 1.31% per degree corrected by regridding. A post-registration spatial filtering technique is presented to reduce noise introduced during registration by selectively attenuating high frequencies near the corners of k-space. Filtering following regridding resulted in reductions in RMS error of 49.6% for simulated data and of 17.4% to 32.5% in human experiments, demonstrating the effectiveness of the filtering technique.

A phased array echoplanar imaging system for fMRI.

A fully parallel, simultaneous sampling phased array receiver system for a clinical echoplanar imaging system is described and evaluated for BOLD activation and relative cerebral blood volume (rCBV) experiments. A 4-coil array curved around the occipital lobe improved SNR by factors of 1.5 in the visual cortex and 3.1 in the visual association cortex relative to a 13-cm diameter surface coil, improving the statistical significance and coverage of visual activation maps. A 4-coil bilateral array increased SNR throughout the head relative to a quadrature head coil by up to a factor of 5 in much of the cortex, with proportional improvement in the SNR of rCBV maps.

[MR imaging of the Achilles tendon: evaluation of criteria for the differentiation of asymptomatic and symptomatic tendons]. / MR-Tomografie der Achillessehne: Evaluation von Kriterien zur Differenzierung von asymptomatischen und symptomatischen Sehnen.

PURPOSE: The purpose of this study was to develop quantitative and qualitative MRI criteria to differentiate between healthy and pathological Achilles tendons. MATERIALS AND METHODS: 364 Achilles tendons were examined on a 1.5 T MRI scanner. 264 patients had Achilles tendon complaints, 100 asymptomatic Achilles tendons served as a control. T 1-weighted, T 2-weighted and a STIR sequence were performed in sagittal and axial orientation. Images were evaluated in consensus by two radiologists. Quantitative and qualitative criteria were assessed. A Mann-Whitney-U-Test and a regression analysis were used for statistical analysis. RESULTS: There were statistically significant differences between the patients with disorders and the control group concerning the depth (12.0 mm and 6.3 mm, p < 0.001) and length (83.2 mm and 45.9 mm, p < 0.001) of the tendon, the area of the tendon cross section (1.60 mm (2) and 061 mm (2), p < 0.001), as well as the length of the bursa retrocalcanea (8.3 mm and 5.3 mm, p < 0.001). There was a sensitivity of 97 % and a specificity of 91 % using a formula including the 3 criteria: tendon depth (A4), length of bursa (A5) and area of tendon (F). CONCLUSION: The measurement of the Achilles tendon and the binary-logistic regression analysis allow differentiation between normal and pathological Achilles tendons.

Barrett's esophagus and active duodenal ulcer: an important clinical association.

A retrospective review of five patients with Barrett's esophagus revealed three with an associated active duodenal ulcer. Two patients also had adrenocarcinoma of the esophagus. Any patient with prolonged gastroesophageal reflux should have careful radiologic and endoscopic evaluation of the entire upper gastrointestinal tract.

Decoupled automated rotational and translational registration for functional MRI time series data: the DART registration algorithm.

A rapid, in-plane image registration algorithm that accurately estimates and corrects for rotational and translational motion is described. This automated, one-pass method achieves its computational efficiency by decoupling the estimation of rotation and translation, allowing the application of rapid cross-correlation and cross-spectrum techniques for the determination of displacement parameters. k-space regridding and modulation techniques are used for image correction as alternatives to linear interpolation. The performance of this method was analyzed with simulations and echo-planar image data from both phantoms and human subjects. The processing time for image registration on a Hewlett-Packard 735/125 is 7.5 s for a 128 x 128 pixel image and 1.7 s for a 64 x 64 pixel image. Imaging phantom data demonstrate the accuracy of the method (mean rotational error, -0.09 degrees; standard deviation = 0.17 degrees; range, -0.44 degrees to +0.31 degrees; mean translational error = -0.035 pixels; standard deviation = 0.054 pixels; range, -0.16 to +0.06 pixels). Registered human functional imaging data demonstrate a significant reduction in motion artifacts such as linear trends in pixel time series and activation artifacts due to stimulus-correlated motion. The advantages of this technique are its noniterative one-pass nature, the reduction in image degradation as compared to previous methods, and the speed of computation.

Sigmoid stricture: an unusual presentation of perforated appendicitis with abscess formation.

Appendicitis is the most common acute surgical condition affecting the abdomen. The manner of onset and location of pain depend, to a great extent, upon the different anatomical positions of the appendix and its proximity to the parietal peritoneum which senses the location of the inflammatory process. When perforation occurs, abscess formation or diffuse peritonitis may develop. We wish to report an unusually rare case of perforated appendicitis with abscess formation presenting clinically and radiologically as a sigmoid stricture.

Successful oral anticoagulant therapy in a patient with short bowel syndrome.

The case of a 41-year-old male with a history of multiple emboli and short bowel syndrome who was successfully anticoagulated with sodium warfarin is described. The prothrombin times were stabilized in a therapeutic range with warfarin doses of 5.0 mg -7.5 mg daily. The pharmacokinetics of warfarin suggests that absorption is high in the proximal intestine. The successful use of sodium warfarin in the patient substantiates this finding and demonstrates that short bowel does not necessarily preclude the use of warfarin for anticoagulation. It is suggested that patients with short bowel syndrome may be successfully anticoagulated with oral products; however, careful monitoring of each patient's prothrombin time is necessary because of the variability and extent of bowel loss.

Regional cerebral blood volume measured by dynamic susceptibility contrast MR imaging in Alzheimer's disease: a principal components analysis.

Dynamic susceptibility contrast (DSC) MRI is an alternative to positron emission tomography (PET) and single photon emission computed tomography (SPECT) for the evaluation of cerebral hemodynamics in patients with Alzheimer's disease. DSC MRI allows the construction of high resolution images of cerebral blood volume (CBV) without the use of radionuclides or ionizing radiation. In this study, DSC MRI data were collected from 16 patients with probable Alzheimer's disease and 16 age-matched control subjects. Characteristic patterns of regional CBV variation were found using principal component analysis. Three such patterns were identified: a global variation pattern, an anterior-to-posterior CBV gradient, and a temporoparietal pattern. Group differences in the principal component scores associated with the global and temporoparietal patterns (P = .08 and P = .007, respectively) suggest that these deficits reflect characteristic CBV abnormalities in Alzheimer's disease. Using only these two scores, the Alzheimer's disease group was classified with a sensitivity of 81% and a specificity of 88%. Additionally, disease severity, as measured by the Mini-Mental State Examination (MMSE), was correlated significantly with the third principal component score (Pearson's r = .50, P = .05).