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.

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.

Quantitative comparison of functional contrast from BOLD-weighted spin-echo and gradient-echo echoplanar imaging at 1.5 Tesla and H2 15O PET in the whole brain.

Spin-echo and gradient-echo echoplanar functional magnetic resonance imaging (fMRI) studies at 1.5 Tesla (T) were used to obtain blood oxygenation level-dependent (BOLD) contrast images of the whole brain in seven strongly right-handed women during execution of a complex motor task. Five subjects underwent subsequent H215O positron emission tomography (PET) studies while performing the same task. Group-averaged results for changes in the MRI relaxation rates R2* and R2 at 1.5T in response to neuronal activation in nine cortical, subcortical, and cerebellar motor regions are reported. Results for each method are grouped according to tissue type-cerebral cortex (precentral gyrus and supplementary motor area), subcortical regions (thalamus and putamen), and cerebellar cortex (superior lobule). The observed changes in R2* from activation-induced oxygenation changes were more variable across brain regions with different tissue characteristics than observed changes in R2. The ratio of deltaR2* to deltaR2 was 3.3 +/- 0.9 for cerebral cortex and 2.0 +/- 0.6 for subcortical tissue. deltaR2*, deltaR2, and relative blood flow changes were deltaR2* = -0.201 +/- 0.040 (s-1), deltaR2 = -0.064 +/- 0.011 s(-1), and deltaf/f = 16.7 +/- 0.8% in the cerebral cortex; deltaR2* = -0.100 +/- 0.026 s(-1), deltaR2 = -0.049 +/- 0.009 s(-1), and deltaf/f = 9.4 +/- 0.7% in the subcortical regions; and deltaR2* = -0.215 +/- 0.093 s(-1), deltaR2 = -0.069 +/- 0.012 s(-1), and deltaf/f = 16.2 +/- 1.2% in the cerebellar cortex.

Comparison of rhyming and word generation with FMRI.

Functional magnetic resonance imaging (FMRI) has been successfully used to non-invasively map language function, but has several disadvantages. These include severe motion sensitivity, which limits overt verbal responses in behavioral paradigms, such as word generation. The lack of overt responses prevents behavioral validation, making data interpretation difficult. Our objective was to compare the FMRI activation patterns of a novel silent rhyme determination task requiring a non-verbal response, to covert word generation from visually presented letters. Five strongly right-handed subjects performed both tasks during multi-slice coronal echo-planar T2*-weighted FMRI. Single subject activation maps were generated for each task by correlation analysis of single pixel time series to a boxcar reference function. These maps for the two tasks were separately interpolated to 256(3), transformed into Talairach space, summed, and thresholded at t>6. Combined activation maps from both tasks showed similar robust perisylvian language area activation, including inferior frontal gyrus, posterior superior temporal lobe, and fusiform gyrus. Subjects performed well on the rhyming task, which activated left hemisphere cortical regions more selectively than the word generation task. The rhyming task showed less activation than the word generation task in areas typically not considered specifically related to language function, such as the dorsolateral prefrontal cortex and anterior cingulate. The rhyming task is a useful tool for brain mapping and clinical applications, potentially more specific to cortical language areas than verbal fluency.

Comparison of fMRI and intraoperative direct cortical stimulation in localization of receptive language areas.

PURPOSE: The purpose of this work was to compare the cortical localization of receptive speech using functional MRI (fMRI) and direct intraoperative electrical stimulation. METHOD: Three strongly right-handed patients with primary neoplasms of the left parasylvian region underwent fMRI while subjected to a passive listening task designed to activate receptive language areas. All three subjects then underwent awake intraoperative language mapping using direct electrical stimulation of the cortex. RESULTS: In all three subjects, similar, but nonidentical, cortical regions were identified as involved in receptive language function by fMRI and direct cortical stimulation mapping. CONCLUSION: fMRI provides excellent receptive language mapping, but its results must be interpreted with caution due to conceptual and technical differences from direct cortical stimulation mapping.

Phase II evaluation of interferon-alpha-2a for progressive or recurrent craniopharyngiomas.

OBJECT: Craniopharyngiomas originate from the same cells as squamous cell skin carcinoma, which can be treated successfully with interferon-alpha (IFNalpha)-2a. The authors evaluated the activity and toxicity of systemic IFN in young patients with craniopharyngiomas. METHODS: Fifteen patients between the ages of 4.2 and 19.8 years who had progressive or recurrent craniopharyngiomas were enrolled in this study. Nine of these patients had never received external-beam radiation therapy. Therapy consisted of 8,000,000 U/m2 IFNalpha-2a administered daily for 16 weeks (induction phase) followed by the same dose three times per week for an additional 32 weeks (maintenance phase). Of the 12 patients who could be evaluated, radiological studies demonstrated a response to treatment in three with predominantly cystic tumors (one minor response, one partial response, and one complete response); one of these patients also showed improvement in visual fields. The size of the cystic component of the tumors often increased temporarily during the first several months of therapy. Three patients met the criteria for progressive disease during therapy. The median time to progression was 25 months. The need for radiation therapy in patients treated with IFN was delayed for 18 to 35 months (median 25 months) in six patients. All patients developed transient flulike symptoms shortly after receiving the first dose of IFN. Other toxicities (predominantly hepatic, neurological, and cutaneous) were seen in nine (60%) of the 15 patients during the first 8 weeks of treatment but resolved after temporary discontinuation and/or dose reduction. CONCLUSIONS: Interferon-alpha-2a is active against some childhood craniopharyngiomas; its toxicity precludes administration of high daily doses, and the optimum dose level and schedule remain to be defined.

Contrast issues in brain tumor imaging.

The utility of gadolinium-based MR imaging contrast agents and iodinated CT contrast agents is discussed in the context of brain tumor imaging. Although contrast materials are routinely administered for brain tumor imaging to improve lesion conspicuity and characterization, the optimal dose and imaging protocols vary according to lesion type and location, the specific clinical situation, and the imaging equipment that is available. Special problems may be encountered in contrast-enhanced imaging of patients with brain tumors who have undergone treatment with surgery, radiation, or chemotherapy.

Depiction of intracranial vessels with MRA: utility of magnetization transfer saturation and gadolinium.

PURPOSE: The purpose of this work was to quantitate the individual and combined effects of magnetization transfer (MT) saturation and gadolinium (Gd) on the visualization of intracranial vessels with MR angiography (MRA). METHOD: Thirty-five subjects underwent two three-dimensional time-of-flight MRA sequences without and with MT and/or Gd. There were 14 MR angiograms without Gd or MT, 18 with MT only, 17 with Gd only, and 21 with both Gd and MT. On a projection image, a region of interest was drawn to delineate the arteries in the middle cerebral artery territory. The total area of blood vessels in the region of interest was calculated for each MR angiogram. Mean vessel areas for the four types of MRA were compared with analysis of variance. RESULTS: MRA with either MT or Gd alone showed significantly more vessel area than MRA without either (p < 0.05). MRA with MT alone and MRA with Gd alone were not different from each other (p = 0.29). The improvement in vessel area measured by using MT and Gd together was significantly more than expected from the cumulative improvement of adding each alone (p < 0.05). CONCLUSION: Combining MT and Gd synergistically improved the visualization of intracranial vessels on MRA.

Temporal bone: comparison of isotropic helical CT and conventional direct axial and coronal CT.

OBJECTIVE: The objective of the study was to compare helical CT (with reformation of coronal images from the axial data set) with conventional direct axial and coronal CT of the temporal bones. SUBJECTS AND METHODS: Nineteen patients underwent both conventional 1-mm direct axial and coronal CT and helical 0.5-mm axial CT. The helical data set was reconstructed at 0.2-mm increments, and axial and coronal images were reconstructed in a plane similar to that of the conventional study, with a slice width of 0.5 mm and 0.5-mm increments. Forty small structures were evaluated independently by three observers, who were unaware of the method of imaging. Observers graded the 40 structures using a modified Likert scale. The graded differences between the two techniques were evaluated using a paired t test. Correlation between observers' gradings was evaluated using analysis of variance. RESULTS: The helical CT technique scored significantly higher than the conventional technique for many individual structures and groups of structures (scutum [p = .041], stapes footplate [p = .006], stapes crura [p = .004], oval window [p = .026], crista falciformis [p = .006], whole temporal bone [P = .012], middle ear [p = .033], inner ear [p = .021], ossicles [p = .044], and stapes [p = .010]). The correlation coefficient among observers was .91 for the whole temporal bone. CONCLUSION: Helical CT using 0.5-mm technique and reconstruction produces diagnostic images comparable with or superior to conventional 1-mm technique because helical CT can obtain thinner slices.

Brain: gadolinium-enhanced fast fluid-attenuated inversion-recovery MR imaging.

PURPOSE: To determine the clinical utility of gadolinium-enhanced fluid-attenuated inversion-recovery (FLAIR) magnetic resonance (MR) imaging of the brain by comparing results with those at gadolinium-enhanced T1-weighted MR imaging with magnetization transfer (MT) saturation. MATERIALS AND METHODS: In 105 consecutive patients referred for gadolinium-enhanced brain imaging, FLAIR and T1-weighted MR imaging with MT saturation were performed before and after administration of gadopentetate dimeglumine (0.1 mmol per kilogram of body weight). Pre- and postcontrast images were evaluated to determine the presence of abnormal contrast enhancement and whether enhancement was more conspicuous with the FLAIR or T1-weighted sequences. RESULTS: Thirty-nine studies showed intracranial contrast enhancement. Postcontrast T1-weighted images with MT saturation showed superior enhancement in 14 studies, whereas postcontrast fast FLAIR images showed superior enhancement in 15 studies. Four cases demonstrated approximately equal contrast enhancement with both sequences. Six cases showed some areas of enhancement better with T1-weighted imaging with MT saturation and other areas better with postcontrast fast FLAIR imaging. Superficial enhancement was typically better seen with postcontrast fast FLAIR imaging. CONCLUSION: Fast FLAIR images have noticeable T1 contrast making gadolinium-induced enhancement visible. Gadolinium enhancement in lesions that are hyperintense on precontrast FLAIR images, such as intraparenchymal tumors, may be better seen on T1-weighted images than on postcontrast fast FLAIR images. However, postcontrast fast FLAIR images may be useful for detecting superficial abnormalities, such as meningeal disease, because they do not demonstrate contrast enhancement of vessels with slow flow as do T1-weighted images.

Dose-intensification of procarbazine, CCNU (lomustine), vincristine (PCV) with peripheral blood stem cell support in young patients with gliomas.

BACKGROUND: The regimen of procarbazine, CCNU, and vincristine is active against gliomas. Previous attempts at dose-intensification have been unsuccessful because of delayed and cumulative myelosuppression. We sought to determine whether peripheral blood stem cell (PBSC) infusions would allow dose-escalation and time compression. PROCEDURE: Eleven patients, age 2.8-35.9 years, with newly diagnosed (n = 10) or recurrent (n = 1) gliomas underwent PBSC harvesting after mobilization with G-CSF. Chemotherapy consisted of CCNU 130 mg/m2 on day 0, vincristine 1.5 mg/m2 on days 0 and 7, and procarbazine 150 mg/m2 on days 1-7. PBSCs were reinfused on day 9 of each course. Four courses of chemotherapy were administered 28 days apart or when counts recovered. Involved field radiation was administered to newly diagnosed high-grade glioma patients following recovery from chemotherapy. RESULTS: Compared to the standard PCV regimen given every 6 weeks, dose intensity received was 1.7- and 1.8-fold greater for CCNU and procarbazine. Chemotherapy was delivered on time in 33/41 (80.5%) courses. Four courses (9.8%) were complicated by absolute neutrophil counts < 200/microL; platelet nadirs < 50,000/microL occurred in two courses (4.9%). Fever with neutropenia complicated three courses. Eight of 9 patients with measurable disease had an objective decrease in tumor size and/or decreased enhancement. Median survival for patients with high-grade gliomas (n = 6) was 13 months. CONCLUSIONS: Dose-intensification of PCV is possible using PBSCs.

Acoustic echoplanar scanner noise and pure tone hearing thresholds: the effects of sequence repetition times and acoustic noise rates.

PURPOSE: Our goal was to determine the effects of acoustic echoplanar scanner noise on pure tone hearing thresholds in normal volunteers and to determine the influence of echoplanar sequence repetition time on threshold effects. METHOD: With use of a calibrated audiometer, pure tones ranging from 125 to 8,000 Hz were delivered monaurally to 10 normal-hearing volunteers in a quiet MR scanner suite and in the presence of acoustic scanner noise produced by three separate single shot blipped echoplanar pulse sequences varying only in repetition time (TR = 1,000, 2,000, or 3,000 ms), with all other parameters including the number of slices held constant. The magnitude of noise-induced threshold changes and the slopes of the threshold curves produced by each of the three echoplanar pulse sequences were then analyzed using multiple comparisons and a least significant difference method. The shapes of the threshold curves produced in each background state were best fit using a quadratic effect for frequency in a mixed effects linear model and compared using F test statistics. RESULTS: All of the volunteers demonstrated entirely normal hearing thresholds throughout the full range of tonal frequencies tested (< 25 dB) when no acoustic scanner noise was present in the scanner suite. Pure tone hearing thresholds significantly increased (p < 0.01) in the presence of acoustic scanner noise, with the magnitude of change inversely proportional to the repetition time and therefore the rate of periodic noise production by the echoplanar sequence used. The shape of the threshold curve in the presence of noise produced by the 1,000 ms TR sequence was not equivalent across the frequency spectrum tested but had a quadratic distribution with peak effects at 750-2,000 Hz. As the repetition time was increased and the periodic noise rate decreased, the magnitude of the noise-induced threshold changes significantly lessened (p < 0.01) and the quadratic distributions of the threshold curves changed significantly (p < 0.01), tending toward a more planar configuration. CONCLUSION: Background acoustic echoplanar scanner noise can significantly increase pure tone thresholds in the optimal frequency hearing range (125-8,000 Hz). However, the threshold effects are not equivalent across the frequency spectrum, and the magnitude of threshold changes is dependent on the rate at which periodic acoustic scanner noises are produced for a given sequence repetition time.

Pearls and pitfalls in clinical neuroradiology.

Imaging technology continues to advance at a rapid pace. Central nervous system imaging, in particular, is an invaluable tool for the practicing clinical neurologist. Although computed tomography (CT) was once the procedure of choice for neuroimaging, CT has been surpassed by magnetic resonance imaging (MRI) because of the latter's greater sensitivity. MRI exquisitely demonstrates brain and spine pathology by means of its multiplanar capability and its ability to generate different tissue contrast with various pulse sequences. However, artifacts as well as normal anatomic variants can mimic significant CNS pathology. An understanding of the technology involved in producing and interpreting these images is necessary in order that protocols can be tailored for each individual patient and that unimportant findings are not misinterpreted as being pathologic. This article will present cases illustrating some of the common neuroimaging artifacts and normal variants as well as important differential diagnoses of certain imaging findings.

FLAIR and HASTE imaging in neurologic diseases.

The need to develop faster imaging techniques has led to the implementation of fast spin-echo imaging, EPI, and hybrid imaging techniques. This article discusses two of these faster imaging techniques, fast fluid-attenuated inversion-recovery (FLAIR) imaging and half-Fourier acquisition single-shot turbo spin-echo (HASTE) imaging, and their potential clinical application in neurologic diseases. FLAIR imaging, in particular, has demonstrated considerable promise for the evaluation of intracranial pathology. HASTE imaging can be used for rapid imaging of the brain or spine in those patients who are claustrophobic or who have difficulty remaining still, but it does not yet have a primary role in clinical neuroradiology.

Imaging features and clinical significance of perineural spread or extension of head and neck tumors.

Perineural spread of head and neck tumors is a form of metastatic disease in which tumor disseminates to noncontiguous regions along the endoneurium or perineurium. Both computed tomography (CT) and magnetic resonance (MR) imaging can help detect perineural spread, although MR imaging is the modality of choice because of its multiplanar capability, its superior soft-tissue contrast, and the decreased amount of artifact from dental hardware. Perineural spread most commonly occurs in adenoid cystic carcinoma and squamous cell carcinoma. Nerve enlargement may lead to foraminal enlargement and, ultimately, to foraminal destruction, findings that are best seen at CT. Extension through the foramen ovale and involvement of the Meckel cave is best seen on coronal T1-weighted MR images, and nerve enhancement is best seen on fat-suppressed T1-weighted MR images. Other radiologic findings include obliteration of fat planes at foraminal openings, neuropathic atrophy, cavernous sinus enlargement, and replacement of the trigeminal subarachnoid cistern with soft tissue. The pathway of perineural tumor spread is predictable with knowledge of the pertinent cranial nerve anatomy; however, patients with radiologically or pathologically proved perineural spread may have normal nerve function at clinical examination. Therefore, it is imperative that the radiologist be familiar with both normal cranial nerve anatomy and the radiologic appearance and assessment of perineural tumor extension.

Cortical activation response to acoustic echo planar scanner noise.

PURPOSE: Our goal was to determine the distribution of auditory and language cortex activation in response to acoustic echo planar scanner noise with functional MRI (fMRI). METHOD: Acoustic scanner noise and spoken text, reproduced on high output cassette tape, were separately delivered at equivalent intensities to six normal hearing adult volunteers through earphones during fMRI data acquisition. In nine other subjects, taped scanner noise was delivered in five successive iterations of the task to assess the consistency of cortical activation to the noise stimulus. Gyri of the auditory and language system were divided into 10 different subregions for analysis of cortical activation. The number of activated pixels and proportion of volunteers activating each cortical subregion were determined using a cross-correlation analysis. RESULTS: Cortical activation to taped acoustic scanner noise was present within the transverse temporal gyrus (primary auditory cortex) in all subjects, but activation was highly variable between subjects in auditory association and language relevant cortex. Auditory association cortex activation was seen in the planum polari, planum temporali, and middle temporal gyrus/superior temporal sulcus regions in one-half to two-thirds of the volunteers. There was no significant difference in the distribution of cortical activation within individual subjects across five successive iterations of the scanner noise task. Listening to spoken text consistently activated primary and association auditory cortex bilaterally as well as language relevant cortex in some cases. The mean number of activated pixels was significantly greater for text listening than acoustic scanner noise in auditory association and language relevant cortical subregions (p < 0.01), although the distribution of activity was similar between the two tasks. CONCLUSION: This preliminary investigation suggests that the complex sounds produced by the echo planar pulse sequence can activate relatively large regions of auditory and language cortex bilaterally, with the extent of activation outside the primary auditory cortex being variable between subjects. However, the distribution of activation within individual subjects was relatively constant across several iterations of the scanner noise stimulus.