Perfusion and permeability MR imaging of gliomas.

Conventional contrast-enhanced MR imaging is the current standard technique for the diagnosis and treatment evaluation of gliomas and other brain neoplasms. However, this method is quite limited in its ability to characterize the complex biology of gliomas and so there is a need to develop more quantitative imaging methods. Perfusion and permeability MR imaging are two such techniques that have shown promise in this regard. This review will highlight the underlying principles, applications, and pitfalls of these evolving advanced MRI methods.

MRI-assessed volume of cerebellum correlates with associative learning.

Richard F. Thompson's cerebellar model of classical eyeblink conditioning highlights Purkinje cells in cerebellar cortex and principal cells in the deep cerebellar nucleus as the integrating cells for acquisition of conditioned responses (CRs). CR acquisition is significantly slower in rabbits with lesions to cerebellar cortex and in Purkinje cell-deficient mice that lose all cerebellar cortical Purkinje cells. Purkinje cells are the largest neurons in the cerebellum and contribute significantly to cerebellar volume. Magnetic resonance imaging (MRI) was used to assess cerebellar volume in humans. Cerebellar volume was related to eyeblink conditioning (400-ms delay procedure) in 8 adults (21-35 years) and compared to 8 older adults (77-95 years) tested previously (Woodruff-Pak, Goldenberg, Downey-Lamb, Boyko, & Lemieux, 2000). In the young adult sample, there was a high correlation between percentage of CRs in a session and cerebellar volume (corrected for total intracranial volume [TIV], r =.58, p =.066). There were statistically significant age differences in cerebellar volume, t(14) = 8.96, p <.001, and percentage of CRs, t(14) = 3.85, p <.002, but no age difference in TIV. Combining the young and older adult sample, the correlation between percentage of CRs and cerebellar volume (corrected for TIV) was.832 (p <.001). Cerebellar volume showed age-related deficits likely due to Purkinje cell loss. Individual differences in classical eyeblink conditioning are associated with differences in cerebellar volume, supporting Thompson's model of a cerebellar cortical role in facilitating this form of associative learning.

Cerebellar volume in humans related to magnitude of classical conditioning.

Neural circuits in the cerebellum are essential for eyeblink classical conditioning, and hippocampal activation is also present during acquisition. Anatomical (volumetric) brain MRI, delay eyeblink conditioning and neuropsychological tests were administered to eight healthy older subjects. The correlation between cerebellar volume (corrected for total cerebral volume) and conditioned response percentage was 0.81 (p < 0.02), but neither hippocampal nor total cerebral volume correlated with conditioning or any neuropsychological test scores. There was no relationship between age and cerebellar volume, but the correlation between hippocampal volume and age was -0.80 (p < 0.02). These volumetric results add to the increasing evidence in humans demonstrating a relationship between the integrity of the cerebellum and eyeblink classical conditioning.

Volume fast spin-echo imaging of the cervical spine.

RATIONALE AND OBJECTIVES: The authors prospectively evaluated a T2-weighted, three-dimensional (3D) volume, fast spin-echo (SE) pulse sequence in assessment of the cervical spine and compared it with standard imaging protocol. MATERIALS AND METHODS: Eighteen patients with neck pain underwent magnetic resonance (MR) imaging at 1.5 T with two-dimensional (2D) fast SE and axial 3D gradient-echo (GRE) protocols and with an additional sagittal T2-weighted volume fast SE protocol. The spinal cord and canal, neural foramina, and intervertebral disks were assessed by two neuroradiologists, and the results were compared with reports from the standard protocol. The quality of the partition (direct sagittal) and reconstructed images were evaluated. RESULTS: No differences existed in the assessment of spinal cord disease or disk herniation with 2D fast SE and volume fast SE imaging. Some mild variation occurred in assessment of the neural foramina. Partition images demonstrated a high level of resolution and contrast, while reconstructed images had consistently lower quality. However, this did not impede detection and grading of disk or spinal abnormalities, which were adequately shown on volume fast SE sagittal images. Neural foramina were well demonstrated on axial reconstructions from volume fast SE imaging. CONCLUSION: Volume fast SE imaging provides information about the spinal cord, canal, disks, and neural foramina that is comparable to the information provided by routine imaging. Its thinner sections and multiplanar reconstruction capability are advantages over 2D imaging. Its greater tissue contrast with better visualization of the cervical cord, greater signal-to-noise ratio, and less susceptibility artifact are advantages over 3D GRE imaging.

Metabolic brain mapping in Alzheimer's disease using proton magnetic resonance spectroscopy.

Alzheimer's disease (AD) is a progressive disorder associated with disruption of neuronal function and neuronal loss. N-acetylaspartate (NAA) is a marker of neuronal content and can be assessed using proton (1H) magnetic resonance spectroscopy (MRS). We utilized 1H-MRS (two-dimensional chemical-shift imaging) to assess amplitudes and areas of NAA, as well as choline moieties (Cho), creatine (Cr) and myo-inositol (mI), in 15 AD patients compared with 14 control subjects. Voxels were classified as predominantly cortical gray matter (CGM), subcortical gray matter (SGM), or white matter (WM). Compared with control subjects, AD patients exhibited decreased NAA/Cho and NAA/Cr amplitudes, whereas an increase was observed in Cho/Cr and in amplitude ratios involving mI. Area ratios were significant in the same direction for NAA/Cho, NAA/Cr, mI/Cr and mI/NAA. No significant effects of tissue type were observed; however, significant group x tissue type interactions were noted for Cho/Cr and mI/Cr amplitudes. Our study confirms that 1H-MRS can identify distinct physicochemical alterations in AD patients, reflecting membrane changes and diminished neuronal function. These alterations can be used as longitudinal markers for the disease.

Intracranial meningiomas: factors that influence the development of cerebral edema after stereotactic radiosurgery and radiation therapy.

PURPOSE: To evaluate causative factors of cerebral edema after stereotactic radiosurgery or stereotactic radiation therapy in intracranial meningiomas. MATERIALS AND METHODS: Of 43 adult patients with intracranial meningiomas, three received 13.5-18-Gy single-fraction stereotactic radiosurgery; one received 19.8 Gy in three fractions, one received 42 Gy in six fractions, and 31 received 32-36 Gy in six to eight fractions of stereotactic radiation therapy; and seven received 45-54-Gy external-beam radiation with 20-28 Gy in five to seven fractions as concomitant stereotactic boosts. Brain edema was estimated by calculating the edema index. RESULTS: After irradiation, all 11 patients with parasagittal and four patients with nonparasagittal tumors developed worsening cerebral edema that necessitated the administration of steroids (P < .001). The statistically significant factors for the development of edema were parasagittal location, presence of pretreatment edema, sagittal sinus occlusion, and the use of more than 6 Gy per fraction. Five patients with parasagittal tumors developed life-threatening panhemispheric edema, which was fatal in one. The causative factors of panhemispheric edema were a large tumor, single-fraction stereotactic radiosurgery, or use of more than 6 Gy per fraction. CONCLUSION: A smaller dose per fraction and aggressive use of steroids may help prevent life-threatening complications due to worsening edema.

Magnetic resonance imaging changes in putamen nuclei iron content and distribution in normal subjects.

To study patterns of iron deposition in the putamen in aging, we reviewed brain magnetic resonance imaging (MRI) scans of 56 normal subjects. We developed the Signal Hypointensity in the Putamen (SHIP) Scale, a semiquantitative measure, to evaluate putamen nuclei for extent of iron deposition relative to the globus pallidus. The SHIP score was highly reliable (kappa = 0.76) and significantly correlated with age (P < 0.0001). We found that age-related iron deposition in putamen nuclei follows a characteristic pattern along a posterolateral-to-anteromedial gradient. This gradient may be related to the microvasculature of the putamen. Other studies are needed to replicate our findings in patients with affective and other neuropsychiatric disorders and to clarify the pathophysiological mechanisms that govern these changes.

Accuracy and reproducibility of brain and tissue volumes using a magnetic resonance segmentation method.

Magnetic resonance (MR) imaging now allows the qualitative and quantitative assessment of the human brain in vivo. As MR imaging resolution has improved, precise measurement of small brain structures has become possible. Methods of measuring brain regions from MR images include both manual and semiautomated methods. Despite the development of numerous volumetric methods, there have been only limited attempts so far to evaluate the accuracy and reproducibility of these methods. In this study we used phantoms to assess the accuracy of the segmentation process. Our results with simple and complex phantoms indicate an error of 3-5% using either manual or semiautomated techniques. We subsequently used manual and semiautomated volumetric methodologies to study human brain structures in vivo in five normal subjects. Supervised segmentation is a semiautomated method that accomplishes the division of MR images into several tissue types based on differences in signal intensity. This technique requires the operator to manually identify points on the MR images that characterize each tissue type, a process known as seeding. However, the use of supervised segmentation to assess the volumes of gray and white matter is subject to pitfalls. Inhomogeneities of the radiofrequency or magnetic fields can result in misclassification of tissue points during the tissue seeding process, limiting the accuracy and reliability of the segmentation process. We used a structured seeding protocol that allowed for field inhomogeneity that produced reduced variation in measured tissue volumes. We used repeated segmentations to assess intra- and inter-rater reliability, and were able to measure small and large regions of interest with a small degree of variation. In addition, we demonstrated that measurements are reproducible with repeat MR acquisitions, with minimal interscan variability. Segmentation methods can accurately and reliably measure subtle morphometric changes, and will prove a boon to the study of neuropsychiatric disorders.

MRI of basilar artery hypoplasia associated with persistent primitive trigeminal artery.

We report three patients with persistent trigeminal arteries, in all of whom the proximal basilar artery was hypoplastic. We draw attention to this common observation, which should not be mistaken for acquired narrowing.

18-Fluorodeoxyglucose positron emission tomography in children and adolescents with traumatic brain injury.

Twenty-two previously normal children and adolescents who suffered a severe, non-penetrating traumatic brain injury had PET during rehabilitation at a median of 1.5 months after the injury. Outcome was assessed at a median of 25 months after brain injury. 16 subjects had CT or MRI within 24 days of PET and 11 subjects had a second PET at the point of outcome (median 28 months after first PET). The PET score (obtained by adding the score of 15 brain regions: normal metabolism = 1; reduced = 0) was significantly associated with the clinical outcome measure. PET earlier than 12 weeks after head trauma correlated with outcome, but later PET did not. PET scores improved significantly between rehabilitation and outcome for the 11 subjects who had two PETs, but improvement was not associated with improvement in clinical condition. PET score did not add to the amount of variance explained in the last regression model for prediction of outcome when the results of contemporaneous CT/MRI and clinical condition were taken into account. The data suggest that routine PET during rehabilitation is no more useful than contemporaneous CT or MRI for prediction of outcome.

Brain choline in depression: in vivo detection of potential pharmacodynamic effects of antidepressant therapy using hydrogen localized spectroscopy.

1. Seven subjects with depression and matched controls were studied using proton spectroscopy to test the hypothesis that choline will be elevated in depression. 2. The proton spectroscopy was repeated after recovery from depression. 3. The study confirmed a state dependent increase in choline in the brain. 4. This change may be used as an in vivo marker of change in depression.

Proton spectroscopy of human brain: effects of age and sex.

1. The present study was done to assess the brain metabolites measured by proton magnetic resonance spectroscopy (MRS) in normal individuals. 2. Proton spectroscopy STEAM voxel technique with chemical shift imaging was used to provide localized metabolic information from the brains of 34 normal volunteers (15 males) between the ages of 21 and 75 years. 3. Choline, Creatine and N-acetyl aspartate (NAA) was lower in white matter than gray matter. Choline/NAA and choline/creatine ratios were also lower in white matter. The choline, creatine and NAA were lower in older subjects in the voxel representing cortical and subcortical gray matter. There were no differences between males and females. 4. This preliminary study suggests that age matching is essential for comparative studies of disease states using proton MRS.

Relative accuracy and reproducibility of regional MRI brain volumes for point-counting methods.

Volumetric magnetic resonance imaging (MRI) methods for the measurement of various neuroanatomical regions are of great interest in studies of neuropsychiatric disorders. Both manual and semiautomated methods have been developed. Manual methods include tracing and point counting. Point counting methods are widely used in post-mortem and microscopy studies. Point counting has been well validated for these purposes. In this article, we report in a series of separate studies the accuracy and reproducibility of point-counting methods. Absolute accuracy was evaluated with a spherical phantom. Accuracy and time efficiency were subsequently assessed with an anatomically realistic phantom and various size grids. The point-counting method was also compared to a tracing method. Finally, the reproducibility of the point-counting method for the caudate and putamen was evaluated on four subjects in a test-retest experiment. These studies provide an estimate of the accuracy and time efficiency of point-counting methods. The test-retest reliability was also high for both caudate and putamen. Findings suggest that point counting is a reliable and efficient method for estimating volumes.

Cyclophosphamide, doxorubicin, vincristine, and prednisone for primary central nervous system lymphoma: short-duration response and multifocal intracerebral recurrence preceding radiotherapy.

The activity of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the treatment of primary central nervous system lymphoma (PCNSL) prior to radiotherapy was studied in six patients. Primary lesions were reduced by 80% or more on contrast-enhancing cross-sectional area in four patients and to a lesser extent in two others after two cycles of chemotherapy. The primary lesion sites demonstrated no contrast enhancement in the three patients who completed four cycles of therapy. However, concurrent with response at the primary disease sites, multiple lesions occurred at distant, noncontiguous CNS parenchymal sites in five patients after two to four cycles of chemotherapy. Median survival was 8.5 months for the six enrolled patients and 16.5 months for the four patients completing craniospinal radiotherapy. PCNSL is highly responsive to standard systemic non-Hodgkin's lymphoma chemotherapy regimens, but the pattern and rapidity of relapse suggest mechanisms of failure including inherent or rapidly evolving antineoplastic drug resistance and perhaps limited drug delivery to occult sites of disease in the brain.

BAEPs in infants with myelomeningocele and later development of Chiari II malformation-related brainstem dysfunction.

Thirty-seven infants with myelomeningocele received brainstem auditory evoked potentials (BAEPs) at a median age of eight days. No infant had brainstem dysfunction at the time of testing. Median follow-up was at 30 months. Of 12 infants who subsequently developed brainstem dysfunction at a median age of three months, 11 had had abnormal neonatal BAEPs. In contrast, only 10 of 25 infants who did not develop brainstem dysfunction had abnormal BAEPs. The mean average I-V interpeak latencies was greater among those who developed symptoms than among those who did not. Neonatal BAEPs can identify a group of asymptomatic infants with myelomeningocele who need close follow-up for the subsequent development of brainstem dysfunction.

Prognostic significance of Ki-67 proliferation index in supratentorial fibrillary astrocytic neoplasms.

Histological grading of fibrillary astrocytic neoplasms has proved to be a valuable prognostic tool, but potentially could benefit from more objective data, such as estimates of proliferative rate. The authors have investigated the prognostic utility of quantitative Ki-67 immunoreactivity in a prospective survival analysis of 36 adult patients with astrocytoma, anaplastic astrocytoma, or glioblastoma multiforme diagnosed between 1987 and 1992. A digital image analyzer was used to assay proliferation indices (PIs) in surgical biopsy specimens obtained at first diagnosis (32 of 36) or at a second biopsy of histologically unchanged high-grade disease (4 of 36). A Ki-67 PI of > or = 7.5% was associated with higher histological grade and poorer survival, and the Ki-67 PI was more significantly related to survival (P < 0.001) than histological grade as determined by a modified Ringertz grading system (P = 0.002). Survival analysis within histological grades suggested that astrocytoma patients with PI > or = 3% may be at increased risk for shorter survival than those with PI < 3%.