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OBJECTIVE. The objective of this article is to discuss the reasons that manuscripts fail to be published and to establish some principles for increasing the likelihood of publication.CONCLUSION. Many good manuscripts fail to be published because they violate a few simple rules for writing a superior journal article. This review presents 10 principles for increasing the likelihood of manuscript publication.

Convection-enhanced delivery is a promising approach to intracerebral drug delivery in which a fluid pressure gradient is used to infuse therapeutic macromolecules through an indwelling catheter into the interstitial spaces of the brain. Our purpose was to test the hypothesis that hyperintense signal changes on T2-weighted images produced by such infusions can be used to track drug distribution.Seven adults with recurrent malignant glioma underwent concurrent intracerebral infusions of the tumor-targeted cytotoxin cintredekin besudotox and 123I-labeled human serum albumin. The agents were administered through a total of 18 catheters among the seven patients. Adequacy of distribution of drug was determined by evidence of distribution of 123I-labeled human serum albumin on SPECT images coregistered with MR images. Qualitative analysis was performed by three blinded observers. Quantitative analysis also was performed.Infusions into 12 catheters produced intraparenchymal distribution as seen on SPECT images, but infusions into six catheters did not. At qualitative assessment of signal changes on MR images, reviewers correctly predicted which catheters would produce extraparenchymal distribution and which catheters would produce parenchymal distribution. Of the 12 infusions that produced intraparenchymal distribution, four catheters had been placed in regions of relatively normal signal intensity and produced regions of newly increased signal intensity, the volume of which highly correlated with the volume and geometry of distribution on SPECT (r2 = 0.9502). Eight infusions that produced intraparenchymal distribution were performed in regions of preexisting hyperintense signal. In these brains, additional signal changes were always produced, but quantitative correlations between areas of newly increased signal intensity and the volume and geometry of distribution on SPECT could not be established.Convection-enhanced infusions frequently do not provide intraparenchymal drug distribution, and these failures can be identified with MRI soon after infusion. When infusions are performed into regions of normal signal intensity, development of hyperintense signal change strongly correlates with the volume and geometry of distribution of infusate.

Schistosomal spinal cord involvement is a rare complication of infection by Schistosoma mansoni. This work reports the MR imaging findings in a patient with schistosomal myelitis involving the lower spinal cord and conus medullaris. MR imaging showed a focal mass with a slightly nodular surface and which had peripheral enhancement after contrast administration. The MR appearance of this complication of schistosomal infection is important to recognize so that early medical therapy can be started in an attempt to maximize neurologic recovery.

OBJECTIVE. A wide variety of antiangiogenic agents have been developed for the treatment of neoplasms. Imaging studies play an important role in assessing the effects of these treatments.CONCLUSION. This review article introduces radiologists to features of these therapies and the most important clinical and preclinical imaging techniques for evaluating antiangiogenic agents.

In this study, the authors sought to investigate the response rate and toxicity of carboplatin in patients with progressive low-grade glioma (LGG). Thirty-two patients with progressive LGG were treated with carboplatin at a dosage of 560 mg/m2. Treatment was given at 4-week intervals and continued until the disease progressed, unacceptable toxicity supervened, or for 12 additional courses after achieving maximal response. Patients with stable disease were treated with a total of 12 cycles. All patients were treated as outpatients. Patients were evaluated for response to treatment and toxicity. All patients received a minimum of two cycles of carboplatin, and were examined for response. A partial response was achieved in nine patients (28%) and a minimal response in two (6%), for an overall response rate of 34% (11 of 32 patients). Eighteen patients (56%) had stable disease. A partial response was achieved in the nine patients after a median of six cycles (range 4-11 cycles), a minimal response was achieved in the two patients after five cycles. Glioma progression was noted in three patients after three, five, and five cycles, respectively. The 11 patients in whom some response was achieved had either an optic pathway tumor or a juvenile pilocytic astrocytoma. Twenty-six of the 32 patients had those characteristics, making the response rate in that group 42% (11 of 26 patients). Thirty-two patients received a total of 387 cycles of chemotherapy. Hematological toxicity was moderate. Twenty-one patients developed thrombocytopenia (platelet count < 50,000/μl); three patients required one platelet transfusion each. Nine patients developed neutropenia (absolute neutrophil count < 500/μl); one developed fever and required administration of antibiotic agents. One dose adjustment in each of the patients prevented further thrombocytopenia and neutropenia. Two patients with stable disease died of respiratory complications. One patient developed Grade III ototoxicity after receiving five cycles, one patient developed hypersensitivity to carboplatin, and none developed nephrotoxicity. Carboplatin given at a dosage of 560 mg/m2 every 4 weeks has activity in patients with progressive LGG. This drug regimen is relatively simple and well tolerated. Further investigation and longer follow-up study are warranted.

Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 study to evaluate this regimen among patients with recurrent WHO grade III malignant glioma (MG).Patients with grade III MG at any recurrence, received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme inducing anti-epileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Clinical assessments were performed monthly and radiographic assessments were obtained at least every 2 months. The primary endpoint was 6-month progression-free survival (PFS) rate.Thirty-nine patients were enrolled. All patients had progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. The median number of episodes of prior progression was 2 (range, 1-7) and the median number of prior treatment regimens was 3 (range, 1-8). With a median follow-up of 82.9 weeks, 24% of patients were progression-free at 6 months. The radiographic response rate was 10%, while 33% achieved stable disease. Among patients who achieved at least stable disease at first evaluation, the 6-month and 12-month PFS rates were 53% and 29%, respectively. The most common grade 3 or greater toxicities were hematologic and complicated less than 4% of administered courses.Imatinib mesylate plus hydroxyurea, is well tolerated and associated with anti-tumor activity in some patients with recurrent grade 3 MG.

The purpose of this study was to correlate the degree of contrast enhancement on dynamic contrast-enhanced T1-weighted MRI and the relative cerebral blood volume (rCBV) values on T2*-weighted MRI in patients with high-grade brain neoplasms.Ten patients with biopsy-proven high-grade gliomas underwent dynamic contrast-enhanced MRI using T1-weighted fast spoiled gradient-echo technique (TR/TE, 8.3/1.5) during i.v. infusion of 0.1 mmol/kg of MR contrast medium. This sequence was followed within 5 minutes by dynamic susceptibility contrast (DSC) imaging (1,500/80) during i.v. infusion of 0.2 mmol/kg of MR contrast medium. Dynamic contrast-enhanced analysis was performed using the maximum-signal-intensity algorithm, and DSC analysis was performed using the negative enhancement integral program. For each tumor, we performed two comparisons: first, the average dynamic contrast-enhanced and rCBV values within a region of interest drawn around the entire contrast-enhancing tumor on a single image through the center of the lesion and, second, the highest dynamic contrast-enhanced and highest rCBV values within each tumor. Statistical analyses of the first comparison were performed using Pearson's correlation coefficient, R2 correlation coefficient, and Spearman's rank correlation and for the second comparison using Kendall's tau correlation.The mean signal intensity values ranged between 3.48 and 7.16 SDs above baseline values (mean, 4.89 SDs). The mean rCBV values ranged between 57.9% and 122.7% of the normal lentiform nucleus (mean, 76.6%). The Pearson's correlation coefficient was 0.867, the R2 correlation coefficient was 0.752, and the Spearman's rank correlation was 0.794 (p = 0.001). Dynamic contrast-enhanced values from the region of highest signal intensity ranged between 7.7 and 48.6 SDs above baseline values (mean, 17.3 SDs). The highest rCBV values ranged between 105% and 400% of the normal lentiform nucleus (mean, 292%). The correlation was estimated to be 0.7778 and was statistically significant at the 0.01 level of statistical significance (p = 0.0035).We found a high correlation between degree of contrast enhancement on dynamic contrast-enhanced images and rCBV values in whole tumors and in regions having the highest degree of contrast enhancement in this small study. Our findings, which suggest that relative permeability and rCBV values may be correlated in high-grade glial neoplasms, deserve further study in a larger patient population.

Results from animal experiments have shown that human IgG2/mouse chimeric antitenascin 81C6 (ch81C6) monoclonal antibody exhibited higher tumor accumulation and enhanced stability compared with its murine parent. Our objective was to determine the effect of these differences on the maximum tolerated dose (MTD), pharmacokinetics, dosimetry, and antitumor activity of (131)I-ch81C6 administered into the surgically created resection cavity (SCRC) of malignant glioma patients.In this phase I trial, eligible patients received a single injection of (131)I-ch81C6 administered through a Rickham catheter into the SCRC. Patients were stratified as newly diagnosed and untreated (stratum A), newly diagnosed after external beam radiotherapy (XRT) (stratum B), and recurrent (stratum C). (131)I-ch81C6 was administered either before (stratum A) or after (stratum B) conventional XRT for newly diagnosed patients. In addition, chemotherapy was prescribed for all patients after (131)I-ch81C6 administration. Dose escalation was performed independently for each stratum. Patients were observed for toxicity and response until death or progressive disease.We treated 47 patients with (131)I-ch81C6 doses up to 4.44 GBq (120 mCi), including 35 with newly diagnosed tumors (strata A and B) and 12 with recurrent disease (stratum C). Dose-limiting hematologic toxicity defined the MTD to be 2.96 GBq (80 mCi) for all patients, regardless of treatment strata. Neurologic dose-limiting toxicity developed in 3 patients; however, none required further surgery to debulk radiation necrosis. Median survival was 88.6 wk and 65.0 wk for newly diagnosed and recurrent patients, respectively.The MTD of (131)I-ch81C6 is 2.96 GBq (80 mCi) because of dose-limiting hematologic toxicity. Although encouraging survival was observed, (131)I-ch81C6 was associated with greater hematologic toxicity, probably due to the enhanced stability of the IgG2 construct, than previously observed with (131)I-murine 81C6.

1Department of Radiology, Duke University Medical Center, Box 3808, Durham, NC 27710. Address correspondence to J. M. Provenzale. he 2005 annual conference of the Academy of Molecular Imaging (AMI), held in Orlando, Florida, on March 18–23, 2005, was a unique forum in which various types of advances in the fields of molecular diagnostics and therapeutics were highlighted. The AMI consists of four institutes, each representing a different facet of molecular imaging. The Institute for Molecular Imaging represents basic scientists in such fields as molecular and cell biology, chemistry, physics, and molecular genetics. The Society for Non-Invasive Imaging in Drug Development represents scientists from academic institutions and industry working in molecular imaging for drug development and testing. The Institute for Clinical PET represents clinical scientists, practicing physicians, and technologists involved in the clinical practices of PET, PET/CT, SPECT, and other imaging sciences related to molecular imaging. The Institute for Molecular Technologies represents corporations involved in invention, manufacture, and provision of molecular imaging devices, products, and services. Thus, the AMI represents a broad spectrum of individuals and institutions concentrated in various types of molecular imaging, ranging from widely accepted practices already in widespread use (e.g., PET and SPECT) to innovative and experimental imaging methods. This article reports some of the novel molecular imaging techniques discussed at the conference that, while still in the various stages of development, may eventually be of clinical importance to radiologists.

The goal of this study was to determine if an iodinated, liposomal contrast agent could be used for high-resolution, micro-CT of low-contrast, small-size vessels in a murine model.A second-generation, liposomal blood pool contrast agent encapsulating a high concentration of iodine (83-105 mg I/mL) was evaluated. A total of five mice weighing between 20 and 28 g were infused with equivalent volume doses (500 microL of contrast agent/25 g of mouse weight) and imaged with our micro-CT system for intervals of up to 240 min postinfusion. The animals were anesthetized, mechanically ventilated, and vital signs monitored allowing for simultaneous cardiac and respiratory gating of image acquisition.Initial enhancement of about 900 H in the aorta was obtained, which decreased to a plateau level of approximately 800 H after 2 hr. Excellent contrast discrimination was shown between the myocardium and cardiac blood pool (650-700 H). No significant nephrogram was identified, indicating the absence of renal clearance of the agent.The liposomal-based iodinated contrast agent shows long residence time in the blood pool, very high attenuation within submillimeter vessels, and no significant renal clearance rendering it an effective contrast agent for murine vascular imaging using a micro-CT scanner.

We sought to examine the relations between age, gender and brain volumes in an elderly population; we also sought to examine ways of measuring these relations. Three sets of analyses were used: correlational analyses, in which correlations between independent variables and brain volumes were calculated without correction for intracranial volume (ICV); covariational analyses, in which ICV was used as a covariate in regression equations; and ratio analyses, in which the dependent variable was the ratio of brain volume to ICV. These analyses yielded similar results, except that (as expected) adjusting for ICV altered estimates of gender differences. Analyses of age showed decreases in left caudate, putamen, and right hippocampus and an increase in CSF, a result generally in accord with previous findings. However, we also found a significant decrease of white-matter volumes and no significant decrease in total gray-matter volumes. Correlational analyses showed that men did not always have larger volumes despite their larger head size; women generally had larger volumes after adjusting for ICV. We found no age-gender interactions.

Purpose We conducted a two-phase clinical trial in patients with progressive malignant glioma (MG). The first phase of this trial was designed to determine the dose of O6-BG effective in producing complete depletion of tumor AGT activity for 48 hours. The second phase of the trial was designed to define the maximum tolerated dose (MTD) of a single dose of temozolomide when combined with O6-BG. In addition, plasma concentrations of O6-BG and O6-benzyl-8-oxoguanine were evaluated after O6-BG. Patients and Methods For our first phase of the clinical trial, patients were scheduled to undergo craniotomy for AGT determination after receiving a 1-hour O6-BG infusion at 120 mg/m2 followed by a continuous infusion at an initial dose of 30 mg/m2/d for 48 hours. The dose of the continuous infusion of O6-BG escalated until tumor AGT was depleted. Once the O6-BG dose was established a separate group of patients was enrolled in the second phase of clinical trial, in which temozolomide, administered as a single dose at the end of the 1-hour O6-BG infusion, was escalated until the MTD was determined. Results The O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. On enrolling 38 patients in six dose levels of temozolomide, the MTD was established at 472 mg/m2 with dose-limiting toxicities limited to myelosuppression. Conclusion This study provides the foundation for a phase II trial of O6-BG plus temozolomide in temozolomide-resistant MG.

OBJECTIVE. In this article, we provide a step-by-step guide to reviewing a manuscript that we hope will improve the quality of reviews for the AJR. CONCLUSION. We have provided a detailed series of guidelines for providing excellent reviews of manuscripts. The template we have provided can be used to serve as a checklist for important questions to ask about manuscripts during the review process. Finally, the principles presented here also can be used as a guide for authors by providing a list of important features to include during manuscript preparation and thereby prospectively address questions that good reviewers are likely to ask. The process of properly reviewing a manuscript is not intuitive but instead requires training and experience, which are not easily acquired. Journal editors depend on highquality reviews and are often faced with reviews that do not quite achieve that desired level. A question the authors of this article asked is, ‘‘How is this experience gained?’’ The answer seemed to be, ‘‘By trial and error,’’ which is not the easiest or most systematic method. In light of these facts, we decided to create a primer on reviewing manuscripts and to disseminate it to our growing team of reviewers by publishing it in the AJR and sending it by e-mail to AJR reviewers. We have also included a template (Appendix 1) that reviewers can use while reviewing a manuscript. The template provides a basic format from which reviewers can systematically proceed through a manuscript and answer important questions. In fact, we encourage reviewers to type their review on the template itself and send their review as an attachment when they submit their review electronically. In addition, the template also serves as a good model for composing a manuscript. In other words, by following this template, authors should be able to compose a well-written manuscript that prospectively addresses the questions good reviewers are likely to ask. Although we provide this primer at risk of insulting our very-well-qualified reviewers, we designed it to be informative for reviewers at any point in their reviewing career. We hope the primer will serve as a good introduction to the review process for new reviewers and also will reinforce subtleties of the review process for experienced reviewers. In doing so, we hope to bring all reviews up to a high standard that is helpful to editors and instructive for authors.

OBJECTIVE. Our purpose is to describe methods of assessing leakiness of the blood-brain barrier and explain mechanisms for exploiting the blood-brain barrier for therapeutic purposes.CONCLUSION. Knowledge of the workings of the blood-brain barrier is important for an understanding of the ways in which blood-brain barrier permeability may be used as a surrogate marker for drug therapeutic response. Manipulation of the blood-brain barrier may provide a means for selectively targeting tumors for drug delivery.

BACKGROUND The authors determined the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of irinotecan (CPT-11), a topoisomerase I inhibitor, when administered with temozolomide among patients with recurrent malignant glioma (MG). METHODS Patients with MG at any recurrence received temozolomide (TMZ) at a dose of 200 mg/m2/day on Days 1–5 plus CPT-11 administered as a 90-minute intravenous infusion during Weeks 1, 2, 4, and 5 of each 6-week cycle. Patients were stratified based on concurrent administration of CYP3A4-inducing anticonvulsants (enzyme-inducing antiepileptic drugs [EIAEDs]). The CPT-11 dose was escalated in successive cohorts of patients independently for each stratum. RESULTS CPT-11, at doses ranging from 40 mg/m2 to 375 mg/m2, was administered with TMZ to 107 patients. Ninety-one patients (85%) had recurrent glioblastoma multiforme (GBM) and 16 (15%) had recurrent anaplastic glioma. Sixty-eight patients (64%) were given EIAEDs. The MTD of CPT-11 for patients concurrently receiving and not receiving EIAEDs was 325 mg/m2 and 125 mg/m2, respectively. The DLTs were hematologic, gastrointestinal, and hepatic. Fifteen patients (14%) achieved either a radiographic complete (n = 5) or partial (n = 10) response across a wide range of CPT-11 dose levels. Patients with recurrent GBM who achieved radiographic response had a median time to disease progression of 54.9 weeks. CONCLUSIONS The current study built on preclinical observations designed to increase the clinical activity of topoisomerase I inhibitors. CPT-11, administered at full dose levels, was well tolerated in combination with TMZ. Furthermore, durable responses were observed in this recurrent population. Ongoing Phase II studies will evaluate the efficacy of this regimen and its application to other malignancies. Cancer 2005. © 2005 American Cancer Society.

To use diffusion-tensor magnetic resonance (MR) imaging to measure involvement of normal-appearing white matter (WM) immediately adjacent to multiple sclerosis (MS) plaques and thus redefine actual plaque size on diffusion-tensor images through comparison with T2-weighted images of equivalent areas in healthy volunteers.Informed consent was not required given the retrospective nature of the study on an anonymized database. The study complied with requirements of the Health Insurance Portability and Accountability Act. Twelve patients with MS (four men, eight women; mean age, 35 years) and 14 healthy volunteers (six men, eight women; mean age, 25 years) were studied. The authors obtained fractional anisotropy (FA) values in MS plaques and in the adjacent normal-appearing WM in patients with MS and in equivalent areas in healthy volunteers. They placed regions of interest (ROIs) around the periphery of plaques and defined the total ROIs (ie, plaques plus peripheral ROIs) as abnormal if their mean FA values were at least 2 standard deviations below those of equivalent ROIs within equivalent regions in healthy volunteers. The combined area of the plaque and the peripheral ROI was compared with the area of the plaque seen on T2-weighted MR images by means of a Student paired t test (P = .05).The mean plaque size on T2-weighted images was 72 mm2 +/- 21 (standard deviation). The mean plaque FA value was 0.285 +/- 0.088 (0.447 +/- 0.069 in healthy volunteers [P.001]; mean percentage reduction in FA in MS plaques, 37%). The mean plaque size on FA maps was 91 mm2 +/- 35, a mean increase of 127% compared with the size of the original plaque on T2-weighted images (P = .03).A significant increase in plaque size was seen when normal-appearing WM was interrogated with diffusion-tensor MR imaging. This imaging technique may represent a more sensitive method of assessing disease burden and may have a future role in determining disease burden and activity.

To prospectively compare diffusion-tensor magnetic resonance (MR) imaging anisotropy measurements of white matter (WM) regions in early and late treatment groups of Krabbe disease patients treated with stem cell transplantation.The study was approved by the Institutional Review Board and was compliant with Health Insurance Portability and Accountability Act; informed consent was obtained from the families of all patients. Patients with early-onset Krabbe disease (four girls and three boys) underwent diffusion-tensor MR imaging before and after stem cell transplantation. Fractional anisotropy (FA) values from serial studies were compared in patients who underwent transplantation at less than 1 month (early group, two girls and one boy) and those who underwent transplantation at 5-8 months (late group, two girls and two boys). FA values were measured in the genu and splenium of the corpus callosum, the frontal WM, and the internal capsule; were compared with those of five age-matched children in the comparison group (normal MR images and no proved neurologic disease); and were expressed as a ratio. Images obtained after transplantation were evaluated at approximately 1 (n = 7), 2 (n = 6), 3 (n = 1), and 4 (n = 1) years.Before transplantation, mean FA ratios in the early group for all four WM regions ranged between 97% and 117%. At 1 year, mean FA ratios at all locations were either 92% or 93%. At 2 years after transplantation, mean FA ratios were between 83% and 92%. In one patient imaged at 3 years, the mean FA ratio was 97%; in another patient imaged at 4 years, the mean FA ratio was 77%. Before transplantation, mean FA ratios in the late group ranged between 55% and 74%. Mean FA ratios were between 37% and 50% at 1 year after transplantation and between 36% and 39% at 2 years.All patients had decreases in FA ratios over time. The early group had higher initial FA ratios and lower subsequent decreases, which may indicate amelioration of the dysmyelinating process.

This article reports on preliminary findings describing microstructural abnormalities in the white matter of cortical areas thought to be associated with bipolar disorder. In all, 14 patients with bipolar disorder and 21 nonpsychiatrically ill control subjects underwent MR imaging including a diffusion tensor imaging (DTI) pulse sequence (six directions, b=1000 mm(2)/s). DTI data were analyzed on a workstation using a program that allowed calculation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) within the following three white matter fiber tracts bilaterally: the orbital frontal cortex, and the superior and middle frontal gyri. These values were compared across patient groups. The left and right orbital frontal white matter exhibited significantly higher ADC values in bipolar subjects than control subjects on both the left (p=0.028) and right (p=0.011). Microstructural changes in the white matter of the orbital frontal areas as reflected by increased ADC values appear to be associated with bipolar disorder. Further research is needed to better understand the interaction of microstructural changes and bipolar symptoms and whether these changes are specific to bipolar disorder.

The objective was to perform dosimetry and evaluate dose-response relationships in newly diagnosed patients with malignant brain tumors treated with direct injections of (131)I-labeled anti-tenascin murine 81C6 monoclonal antibody (mAb) into surgically created resection cavities (SCRCs) followed by conventional external-beam radiotherapy and chemotherapy.Absorbed doses to the 2-cm-thick shell, measured from the margins of the resection cavity interface, were estimated for 33 patients with primary brain tumors. MRI/SPECT registrations were used to assess the distribution of the radiolabeled mAb in brain parenchyma. Results from biopsies obtained from 15 patients were classified as tumor, radionecrosis, or tumor and radionecrosis, and these were correlated with absorbed dose and dose rate. Also, MRI/PET registrations were used to assess radiographic progression among patients.This therapeutic strategy yielded a median survival of 86 and 79 wk for all patients and glioblastoma multiforme (GBM) patients, respectively. The average SCRC residence time of (131)I-mu81C6 mAb was 76 h (range, 34-169 h). The average absorbed dose to the 2-cm cavity margins was 48 Gy (range, 25-116 Gy) for all patients and 51 Gy (range, 27-116 Gy) for GBM patients. In MRI/SPECT registrations, we observed a preferential distribution of (131)I-mu81C6 mAb through regions of vasogenic edema. An analysis of the relationship between the absorbed dose and dose rate and the first biopsy results yielded a most favorable absorbed dose of 44 Gy. A correlation between decreased survival and irreversible neurotoxicity was noted. A comparative analysis, in terms of median survival, was performed with previous brachytherapy clinical studies, which showed a proportional relationship between the average boost absorbed dose and the median survival.This study shows that (131)I-mu81C6 mAb increases the median survival of GBM patients. An optimal absorbed dose of 44 Gy to the 2-cm cavity margins is suggested to reduce the incidence of neurologic toxicity. Further clinical studies are warranted to determine the effectiveness of (131)I-mu81C6 mAb based on a target dose of 44 Gy rather than a fixed administered activity.

background Infantile Krabbe’s disease produces progressive neurologic deterioration and death in early childhood. We hypothesized that transplantation of umbilical-cord blood from unrelated donors before the development of symptoms would favorably alter the natural history of the disease among newborns in whom the disease was diagnosed because of a family history. We compared the outcomes among these newborns with the outcomes among infants who underwent transplantation after the development of symptoms and with the outcomes in an untreated cohort of affected children. methods Eleven asymptomatic newborns (age range, 12 to 44 days) and 14 symptomatic infants (age range, 142 to 352 days) with infantile Krabbe’s disease underwent transplantation of umbilical-cord blood from unrelated donors after myeloablative chemotherapy. Engraftment, survival, and neurodevelopmental function were evaluated longitudinally for four months to six years. results The rates of donor-cell engraftment and survival were 100 percent and 100 percent, respectively, among the asymptomatic newborns (median follow-up, 3.0 years) and 100 percent and 43 percent, respectively, among the symptomatic infants (median follow-up, 3.4 years). Surviving patients showed durable engraftment of donor-derived hematopoietic cells with restoration of normal blood galactocerebrosidase levels. Infants who underwent transplantation before the development of symptoms showed progressive central myelination and continued gains in developmental skills, and most had age-appropriate cognitive function and receptive language skills, but a few had mildto-moderate delays in expressive language and mild-to-severe delays in gross motor function. Children who underwent transplantation after the onset of symptoms had minimal neurologic improvement. conclusions Transplantation of umbilical-cord blood from unrelated donors in newborns with infantile Krabbe’s disease favorably altered the natural history of the disease. Transplantation in babies after symptoms had developed did not result in substantive neurologic improvement.

Numerous studies have shown gender differences in the brain volumes of elderly adults. Some evidence shows that higher estrogen levels may be neuroprotective, suggesting that hormone therapy (HT) may in part be responsible for these gender differences; however, few studies have examined the relation between HT and brain volumes. Brain volumes of caudate, putamen, hippocampus, gray matter, white matter, white-matter lesions, and cerebrospinal fluid were measured on magnetic resonance imaging scans. A comprehensive neuropsychological battery was administered. Women were separated into two groups based on HT use, and we used multiple regression analyses to compare these groups with one another and with men. Results of brain-volume measurements showed that HT users had significantly less gray matter and more cerebrospinal fluid than nonusers. Results of the neuropsychological testing showed that HT users performed better on the Shipley Vocabulary Test than males did.

To determine prospectively the diffusibility of water in normal lumbar disks in adults by using the mean apparent diffusion coefficient (ADC) and to determine if a relationship exists between disk ADC and magnetic resonance (MR) findings of disk degeneration.The study was approved by the Institutional Review Board, and all participants gave written informed consent prior to enrollment. Diffusion-weighted MR imaging of the lumbar spine was performed in 39 patients (all men; mean age, 53 years) and five volunteers (all men; mean age, 31 years). ADC values were recorded for each disk. All disks were visually graded by two independent observers as being normal or as showing at least one of three MR findings of degeneration on sagittal T2-weighted images. Mean ADC values of normal disks were compared with those of degenerated disks and were correlated with age and anatomic location. Data were analyzed by using Kendall correlation statistics, Mantel-Haenszel statistics, and a paired two-tailed Student t test.The mean ADC value was 2.27 x 10(-3) mm(2)/sec +/- 0.58 (+/- standard deviation) in normal disks and 2.06 x 10(-3) mm(2)/sec +/- 0.47 in abnormal disks (9% reduction, P = .006). A statistically significant dependence of lumbar disk ADC on anatomic location was reported (analysis of variance, P.001), with lower ADC values seen in more caudal disks. There was no association between age and mean disk ADC.A statistically significant decrease was seen in the ADC values of degenerated lumbar disks when compared with ADC values of normal disks. More caudal disks, even when normal, showed lower ADC values than more cephalic disks.

sion. Because seizures are an uncommon presenting feature of intracranial aneurysms, aneurysm is generally not considered in the differential diagnosis of lesions causing seizures. Aneurysms can produce seizures by a number of mechanisms. including compression or infarction of adjacent brain tissue as well as irritation by blood products from subclinical hemorrhage I 1-3]. We present the MR imaging findings in two patients with cerebral aneurysms and seizures in the absence of clinical features of aneurysm rupture. In both cases. we saw abnormal perianeurysmal MR signal within the adjacent temporal lobe, and the MR signal abnormality was associated with findings at surgery of gliotic brain tissue. In one of these patients, who had thrombus found outside the aneurysm at surgery. the abnormal MR signal also indicated subclinical leakage of the aneurysm. We therefore suggest that the finding of perianeurysmal MR signal abnormality should raise the possibility that an aneurysm has caused structural changes in the adjacent brain and serve as evidence to support the role of an aneurysm in producing seizures in individual patients.

A 60-year-old man developed hemiballismus due to an intracranial hemorrhage involving the subthalamic nucleus 8 weeks after orthotopic liver transplantation. The hemorrhage was thought to be due to alterations in cerebral blood flow following a period of hypotensive shock due to sepsis, in the presence of anticoagulant therapy and thrombocytopenia. This represents a rare neurologic complication of liver transplantation.

We present the clinical and neuroradiologic findings of a 31-year-old man with Kearns-Sayre syndrome- related dilated cardiomyopathy who experienced a left middle cerebral artery territory stroke, thought to be due to cardiogenic embolism. The rate of clinically apparent cardiomyopathy in Kearns-Sayre patients can be expected to increase as their survival is prolonged by the use of cardiac pacemaker devices. Under these circumstances, stroke caused by cardiogenic embolism, which is presently rare, may become more common.

The purpose of this study was to assess the clinical and radiologic features of tumor progression in children with trilateral retinoblastoma.Clinical records of eight children with trilateral retinoblastoma were reviewed for the patient's age at the time of diagnosis of the ocular tumor, time interval from diagnosis of ocular retinoblastoma to discovery of the intracranial tumor, time interval from diagnosis of retinoblastoma to death, and time interval from diagnosis of the intracranial tumor to death. CT or MRI studies were reviewed for the appearance of the primary intracranial neoplasm, intracranial metastases, and spinal metastases.The mean age of the patients at diagnosis of bilateral retinoblastoma was 4.5 months, and the mean age at diagnosis of the intracranial midline tumor was 26 months. The mean interval from the time of diagnosis of retinoblastoma to discovery of the intracranial tumor was 21.5 months. Two children had spinal leptomeningeal metastases at the time of discovery of the midline intracranial mass although no intracranial metastases were seen on imaging. In the other children, intracranial and spinal leptomeningeal metastases frequently developed within months of the diagnosis of retinoblastoma despite lack of progression in the midline intracranial lesion. Six children died of leptomeningeal spread of tumor. The mean interval from diagnosis of the ocular tumor to death was 46 months and from diagnosis of the intracranial tumor to death was 17 months. One child developed metastatic retinoblastoma in the ulna 10 years after the diagnosis of the intracranial tumor.Children typically died of leptomeningeal tumor dissemination despite lack of progression in the midline intracranial mass. Effective treatment of trilateral retinoblastoma may require close evaluation of these children for leptomeningeal dissemination.

We used diffusion tensor MRI to redefine the size of multiple sclerosis (MS) plaques on fractional anisotropy (FA) maps.Thirty-six white matter (WM) plaques were identified in 20 patients with MS. Plaque FA was measured by placing regions of interest (ROIs) on plaques on diffusion tensor images. We compared FA values in identical mirror-image ROIs placed on normal-appearing WM in the contralateral hemisphere. This comparison showed a mean decrease in FA of 41% in plaques, serving as the threshold for outlining abnormal regions in normal-appearing WM surrounding plaques. ROIs were placed around each plaque and FA values were compared with those in the mirror-image ROIs. Combined areas of perilesional normal-appearing WM with 40% or more FA reduction plus plaque were compared with the areas of abnormality on T2-weighted images using a paired Student's t test. A p value of 0.05 or less was considered significant.Mean plaque area was 60 mm(2) (range, 15-103 mm(2)), mean plaque FA was 0.251 (range, 0.133-0.436), and mean FA of contralateral normal-appearing WM was 0.429 (range, 0.204-0.712). Applying a threshold of 40% FA reduction, mean combined area of abnormal WM (including plaque seen on T2-weighted sequences) was 87 mm(2) (range, 30-251 mm(2)) or 145% of the mean plaque area that was seen on T2-weighted images (p0.001).Using an operator-defined threshold of abnormal FA values based on plaque anisotropy characteristics, we saw a statistically significant increase in plaque size.

The purpose of this study was to determine whether microstructural abnormalities in the white matter of the dorsolateral prefrontal cortex are associated with late-life depression.Seventeen elderly depressed subjects were compared with 16 elderly subjects who were not depressed. Diffusion tensor imaging was used to measure the fractional anisotropy of the white matter in the dorsolateral prefrontal cortex's superior and middle frontal gyri bilaterally and in the left occipital lobe as a control region. The authors compared results between groups while controlling for age, sex, and comorbid medical disorders.Even after controlling for age, sex, hypertension, and heart disease, the authors found significantly lower fractional anisotropy values in the right superior frontal gyrus white matter of depressed patients than comparison subjects.Microstructural changes in the white matter of the right superior frontal gyrus are associated with late-life depression. Further work is needed to determine how these changes contribute to depression outcomes.

To retrospectively measure the diffusion-weighted (DW) imaging characteristics of peritumoral hyperintense white matter (WM) and peritumoral normal-appearing WM, as seen on T2-weighted magnetic resonance (MR) images of infiltrative high-grade gliomas and meningiomas.Seventeen patients with biopsy-proved glioma and nine patients with imaging findings consistent with meningioma and an adjacent hyperintense region on T2-weighted MR images were examined with DW and diffusion-tensor MR imaging. Apparent diffusion coefficients (ADCs) were measured on maps generated from isotropic DW images of enhancing tumor, hyperintense regions adjacent to enhancing tumor, normal-appearing WM adjacent to hyperintense regions, and analogous locations in the contralateral WM corresponding to these areas. Fractional anisotropy (FA) was measured in similar locations on maps generated from diffusion-tensor imaging data. Changes in ADC and FA in each type of tissue were compared across tumor types by using a two-sample t test. P.05 indicated statistical significance.Mean ADCs in peritumoral hyperintense regions were 1.309 x 10(-3) mm2/sec (mean percentage of 181% of normal WM) for gliomas and 1.427 x 10(-3) mm2/sec (192% of normal value) for meningiomas (no significant difference). Mean ADCs in peritumoral normal-appearing WM were 0.723 x 10(-3) mm2/sec (106% of normal value) for gliomas and 0.743 x 10(-3) mm2/sec (102% of normal value) for meningiomas (no significant difference). Mean FA values in peritumoral hyperintense regions were 0.178 (43% of normal WM value) for gliomas and 0.224 (65% of normal value) for meningiomas (P =.05). Mean FA values for peritumoral normal-appearing WM were 0.375 (83% of normal value) for gliomas and 0.404 (100% of normal value) for meningiomas (P =.01).The difference in FA decreases in peritumoral normal-appearing WM between gliomas and meningiomas was significant, and the difference in FA decreases in peritumoral hyperintense regions between these tumors approached but did not reach significance. These findings may indicate a role for diffusion MR imaging in the detection of tumoral infiltration that is not visible on conventional MR images.

We used functional magnetic resonance imaging (fMRI) of a visual target detection (oddball) task to investigate age differences in neural activation for the detection of two types of infrequent events: visually simple items requiring a response shift (targets) and visually complex items that did not entail a response shift (novels). Targets activated several prefrontal regions (e.g. middle frontal gyrus), as well as deep gray matter regions (caudate, putamen, thalamus and insula). Prefrontal activation was similar for younger and older adults, whereas deep gray matter activation was relatively greater for the older adults. Novels activated occipital regions (fusiform and lateral occipital gyri), and this activation was relatively reduced for older adults. The changes in behavioral performance across the task conditions were similar for the two age groups, although the older adults’ responses were slower overall. Regression analyses of the relation between neural activation and task performance (response time) indicated that whereas performance was mediated most directly by prefrontal cortex for younger adults, older adults’ performance was influenced to a greater extent by deep gray matter structures. Older adults may place relatively greater emphasis on the attentional control of response regulation, in compensation for the age-related decline in visual processing efficiency.

Irinotecan is a topoisomerase I inhibitor previously shown to be active in the treatment of malignant glioma. We now report the results of a phase 1 trial of irinotecan plus BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, for patients with recurrent or progressive MG. Irinotecan dose escalation occurred independently within 2 strata: patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) and patients not receiving EIAEDs. BCNU was administered at a dose of 100 mg/m2 over 1 h every 6 weeks on the same day as the first irinotecan dose was administered. Irinotecan was administered intravenously over 90 min once weekly. Treatment cycles consisted of 4 weekly administrations of irinotecan followed by a 2-week rest with dose escalation in cohorts of 3 to 6 patients. Seventy-three patients were treated, including 49 patients who were on EIAEDs and 24 who were not on EIAEDs. The maximum tolerated dose for patients not on EIAEDs was 125 mg/m2. The maximum tolerated dose for patients on EIAEDs was 225 mg/m2. Dose-limiting toxicity was evenly distributed among the following organ systems: pulmonary, gastrointestinal, cardiovascular, neurologic, infectious, and hematologic, without a clear predominance of toxicity involving any one organ system. There was no evidence of increasing incidence of toxicity involving one organ system as irinotecan dose was escalated. On the basis of these results, we conclude that the recommended doses of irinotecan for a phase 2 clinical trial when given in combination with BCNU (100 mg/m2) are 225 mg/m2 for patients on EIAEDs and 125 mg/m2 for patients not on EIAEDs.

BACKGROUND AND PURPOSE: Compared with MR imaging, dynamic CT perfusion imaging covers only a fraction of the whole brain. An important assumption is that CT perfusion abnormalities correlate with total ischemic volume. The purpose of our study was to measure the degree of correlation between abnormalities seen on CT perfusion scans and the volumes of abnormality seen on MR diffusion and perfusion images in patients with acute large-vessel stroke. METHODS: Fourteen patients with acute hemispheric stroke symptoms less than 12 hours in duration were studied with single-slice CT perfusion imaging and multislice MR diffusion and perfusion imaging. CT and MR perfusion studies were completed within 2.5 hours of one another (mean, 77 minutes) and were reviewed independently by two neuroradiologists. Hemodynamic parameters included cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). Extents of abnormality on images were compared by using Kendall correlation. RESULTS: Statistically significant correlation was found between CT-CBF and MR-CBF abnormalities (τ = 0.60, P = .003) and CT-MTT and MR-MTT abnormalities (τ = 0.65, P = .001). Correlation of CT-CBV with MR-CBV approached significance (τ = 0.39, P = .06). Extent of initial hyperintensity on diffusion-weighted images correlated best with extent of MR-CBV abnormality (τ = 0.69, P = .001), extent of MR-MTT abnormality (τ = 0.67, P = .002), and extent of CT-CBV abnormality (τ = 0.47, P = .02). CONCLUSION: Good correlation was seen between CT and MR for CBF and MTT abnormalities. It remains uncertain whether CT perfusion CBV abnormalities correspond well to whole-brain abnormalities.

Diffusion tensor imaging (DTI) measures the displacement of water molecules across tissue components, thus providing information regarding the microstructure of cerebral white matter. Fractional anisotropy (FA), the degree to which diffusion is directionally dependent, is typically higher for compact, homogeneous fiber bundles such as the corpus callosum. Previous DTI studies in adults have demonstrated an age-related decline in white matter FA, but whether the relation between FA and behavioral performance varies as a function of age has not been determined. We investigated adult age differences in FA, and age-related changes in the relation between FA and response time (RT), in a visual target-detection task. The results confirmed that, independently of age, FA is higher in the corpus callosum than in other brain regions. We also observed an age-related decline in FA that did not vary significantly across the brain regions. For both age groups, a lower level of integrity of the cerebral white matter (as indexed by FA), in specific brain regions, was associated with slower responses in the visual task. An age-related change in this relation was evident, however, in that the best predictor of RT for younger adults was FA in the splenium of the corpus callosum, whereas for older adults the best predictor was FA in the anterior limb of the internal capsule. This pattern is consistent with measures of the task-related cortical activation obtained from these same individuals and suggests an age-related increase in the attentional control of responses mediated by corticostriatal or corticothalamic circuits.

The purpose of the study was to examine change in volume of hyperintense white matter lesions in a cohort of community-dwelling elderly subjects without neuropsychiatric disease. SUBJECTS AND METHODS. One hundred seventeen volunteers underwent brain MR imaging on a 1.5-T scanner. Demographic data and the presence of specific medical illnesses were recorded at the time of the initial scanning. Hyperintense white matter lesion volume was measured using a supervised semiautomated technique that seeded lesions and then created a segmented lesion image. Subjects underwent repeated MR imaging at a mean of 25 months. Mean change in lesion volume and mean percentage of change were determined between the two time points. Logistic regression models were used to examine the differential effects of age, sex, race, and self-reported medical morbidity.Mean baseline volume of cerebral hyperintense lesions was 4.91 cc, and at 2-year follow-up, it was 6.42 cm(2) (p0.0001), for a mean increase of 26.7%. Comparable results were seen in separate analyses of hemispheric hyperintense lesion volumes. Neither sex, race, nor baseline hyperintense lesion volume was significantly associated with an interval increase in lesion volume. Age (p = 0.0117) and presence of diabetes (p = 0.0215) were associated with greater change.Elderly subjects exhibited approximately a 27% increase in hyperintense lesion volume over a 2-year period, a finding influenced by both age and medical comorbidity rates. Because hyperintense lesions can be associated with several neuropsychiatric conditions, further research is needed to determine if interventions designed to slow hyperintense lesion disease progression may improve neuropsychiatric outcomes.

Background There is a substantial body of research supporting the vascular depression hypothesis of late-life depression. To update this hypothesis so it incorporates recent research, we propose that the term subcortical ischemic vascular depression may be a more accurate representation of the disease process. We sought to investigate this diagnosis as a construct by examining differences between depressed subjects with and without magnetic resonance imaging defined subcortical ischemic vascular depression. Methods This case-control study examined 139 depressed elderly subjects. Demographic data, psychiatric, medical, and family history, depressive symptomatology, and functional impairment were compared between groups dichotomized based on neuroimaging findings. Results Seventy-five (54%) of the subjects met neuroimaging criteria for subcortical ischemic vascular depression. Age was most strongly associated with increased prevalence of subcortical ischemic vascular depression. Lassitude and a history of hypertension were also positively associated with the diagnosis; a family history of mental illness and loss of libido were negatively associated with the diagnosis. Conclusions These data support that subcortical ischemic vascular depression may be a specific syndrome from other types of late-life depression. Further research is needed to further characterize this disorder, particularly in regards to cognitive function and treatment implications.

Positron emission tomography data (Madden, Langley, et al., 2002) were analyzed to investigate adult age differences in the relation between neural activation and the lexical (word frequency) and sublexical (word length) components of visual word identification. The differential influence of these components on reaction time (RT) for word/nonword discrimination (lexical decision) was generally similar for the two age groups, with word frequency accounting for a greater proportion of lexical decision RT variance relative to word length. The influence of word length on RT, however, was relatively greater for older adults. Activation in regions of the ventral occipito-temporal cortex was related to the RT changes associated with word frequency and length for older adults, but not for younger adults. Specifically, older adults' frequency effects were related to activation in both anterior (Brodmann's area [BA] 37) and posterior (BAs 17 and 18) regions of the occipito-temporal pathway, whereas word length effects were only associated with posterior activation (BA 17). We conclude that aging affects the neural mechanisms supporting word identification performance although behavioral measures of this ability are generally constant as a function of age.

Objective: Deep white matter hyperintense lesions are associated with advanced age and late-life depression. The authors examined where age-related cerebral lesions occurred in elderly depressed and healthy control subjects. Methods: Eighty-seven depressed subjects and 47 control subjects underwent 1.5 T cranial magnetic resonance imaging (MRI). Utilizing a semiautomated method, a segmented image was created containing only white matter lesions. We created a statistical parametric map (SPM) separately for each subject group that displayed the association between lesions in any voxel and advanced age. Results: The SPM analysis in depressed subjects demonstrates a significant association between age and lesions found in bilateral, frontal, and left parietal regions. The analysis in control subjects found significant associations only in bilateral parieto-temporal regions, not frontal regions. Conclusions: This study demonstrates a different pattern of age-related lesion location between depressed and control subjects. It further supports the theory that frontostriatal disconnection contributes to late-life depression.

Anisotropy measurements were obtained from periventricular foci of T2 prolongation and adjacent normal-appearing white matter in a case of B12 leukoencephalopathy. Measurements were compared with mean values from two age-matched control subjects. Anisotropy was greatly reduced in the lesions evident on T2-weighted images and in the normal-appearing adjacent white matter (WM), indicating that the extent of WM tract disruption was greater than could be identified on routine MR sequences.

BACKGROUND AND PURPOSE: The potential pitfalls in the diagnosis of dural sinus thrombosis include the presence of arachnoid granulations, intrasinus fibrotic bands (so-called septa), and hypoplasia or aplasia of the dural sinuses. The purpose of this study was to assess the appearance, distribution, and prevalence of arachnoid granulations and septa in the dural sinuses by using a high resolution 3D contrast-enhanced magnetization prepared rapid acquisition gradient-echo (MPRAGE) imaging sequence. METHODS: Conventional MR images and contrast-enhanced MPRAGE images of 100 consecutive patients who had no abnormalities of the dural sinuses were retrospectively reviewed. The incidence, site, number, size, signal intensity, and shape of arachnoid granulations and septa within the sinuses and their relationship with adjacent veins were recorded. RESULTS: With 3D contrast-enhanced MPRAGE imaging, 433 round, oval, or lobulated focal filling defects were found in a total of 90 patients. Curvilinear septa were observed in 92 patients. Sixty-nine patients had round, oval, or lobulated defects in the transverse sinus, 59 had such defects in the superior sagittal sinus, and 47 had such defects in the straight sinus. All except two of the above defects were isointense relative to CSF on all images. These structures were presumed to be arachnoid granulations. Of 431 arachnoid granulations, 233 (53.8%) were located in the superior sagittal sinus, 122 (28.1%) in the transverse sinus, and 76 (17.6%) in the straight sinus. One or more veins were seen to enter arachnoid granulations in 414 (96%) instances. CONCLUSION: The contrast-enhanced 3D MPRAGE imaging sequence showed a much higher prevalence and a different distribution of arachnoid granulations and septa within dural sinuses than have been observed in previous radiologic studies. Arachnoid granulations were closely related spatially to veins.

The purpose of the study was to consider MRI hyperintensities as a potential endophenotype for bipolar disorder (BPD) and to investigate Notch3 (CADASIL) as a candidate gene for BPD. MRI scans were performed on 21 members of a family with a high incidence of BPD. Two-point and multipoint linkage analyses were performed and two exons of Notch3 were investigated with SSCP. Fifteen of 21 family members had MRI hyperintensities, including all bipolar patients and six family members with no affective illness. Two-point linkage analysis yielded negative results for all models. Multipoint linkage analysis yielded negative results except for Model 1a, in which a maximal LOD score was −1.24. A mutation screen of Exons 3 and 4 was negative. Notch3 does not appear to be a candidate gene for BPD in this family. © 2002 Wiley-Liss, Inc.

Brain magnetic resonance imaging (MRI) allows for quantitative assessment of hyperintense foci, which are seen with aging and various diseases. These foci, considered to represent lesions, are important in the study of various psychiatric illnesses, including depression. Few quantitative measures have been developed for such research. The goal of the current study was to develop a reliable and efficient method for quantifying the volumes of gray and white matter lesions in MRI scans of the elderly. Interrater reliability was determined by repeat lesion measures on 16 scans. Semi-automated segmentation was performed that identified potential lesions, and then lesions were manually selected based upon detailed anatomic criteria. The lesion quantification procedure took between 25 and 45 min per scan. Reliability intraclass correlation coefficients (ICCs) were 0.99 for both gray and white matter lesions. Volumetric results were found to be moderately correlated with previous lesion ratings (r-values between 0.37 and 0.62, P

Whether or not severe febrile seizures in infancy cause hippocampal injury and subsequent medial temporal sclerosis is an often debated question in epilepsy. Recent magnetic resonance imaging (MRI) of infants suffering from febrile seizures has provided preliminary evidence that abnormally increased T2 signal intensity can be seen in the hippocampi of infants following prolonged and focal febrile seizures. Follow-up MRIs in a few of these infants have confirmed that medial temporal sclerosis can develop following these acute MRI signal changes. In this article, we review the hypotheses and MRI evidence relating to hippocampal injury during prolonged febrile seizures and the later development of medial temporal sclerosis.

Adult age differences in the neural systems mediating semantic (context-independent) memory were investigated using positron emission tomography (PET). Younger (20–29 years) and older (62–70 years) participants performed lexical decision (word/nonword discrimination) and nonsemantic (simple visual search) baseline tasks during PET scanning. Within the lexical decision task, display duration and presentation rate were varied across scans. The behavioral data suggested that although an age-related slowing was evident in visual feature and response processing, the retrieval of semantic/lexical information was similar for younger and older adults. For both age groups, lexical-related activation occurred in inferior prefrontal and occipitotemporal regions of the left hemisphere. Differential activation, as a function of age group, was observed in the left occipitotemporal pathway as a result of older adults' maintaining higher levels of neural activity in striate cortex (during visual search) and in inferior temporal cortex (during lexical decision). The prefrontal activation was similar for the two age groups. Thus, although this form of semantic memory retrieval does not undergo significant age-related decline, an age-related change in the associated pattern of neural activation is evident. These findings differ from previous neuroimaging studies of episodic (context-dependent) memory retrieval, which have suggested that age-related compensatory mechanisms are expressed primarily by greater activation of prefrontal regions for older adults than for younger adults.

We evaluated commercially available software that rapidly and automatically registers brain MR images on a clinical workstation, and we studied the accuracy of these registrations.Ten patients with a diagnosis of glioblastoma multiforme underwent contrast-enhanced inversion recovery prepared three-dimensional (3D) volumetric spoiled gradient-recalled acquisition in the steady state (SPGR) MR imaging (contiguous 1.5-mm slice thickness, 96-104 slices). After this imaging sequence, each patient was brought out of the head coil into a sitting position and then repositioned in the coil. The inversion recovery prepared 3D SPGR sequence was then repeated. A commercially available software program operating on a clinical workstation was used to automatically register the second inversion recovery prepared SPGR series to the first. The speed of registration was recorded. The accuracy of each registration was estimated by recording the coordinates of eight anatomic landmarks on the registered and reference series and by calculating the mean error among matching landmarks.In nine of 10 patients, the registration software produced a visually satisfactory registration. In one patient, a second registration was necessary to produce a satisfactory registration. The processing time for each iteration was 48.3 +/- 3.8 sec (mean +/- SD). The mean error in aligning matching anatomic landmarks ranged from 0.67 to 1.41 mm, with an overall mean of 1.18 mm. The largest error among matching landmarks was 2.3 mm.Commercially available registration software can automatically register 3D imaging volumes in less than 1 min. The mean error in registration was approximately equivalent to the dimensions of a single voxel.

PURPOSE: We conducted a phase II trial of carmustine (BCNU) plus the O6-alkylguanine-DNA alkyltransferase inhibitor O6-benzylguanine (O6-BG) to define the activity and toxicity of this regimen in the treatment of adults with progressive or recurrent malignant glioma resistant to nitrosoureas. PATIENTS AND METHODS: Patients were treated with O6-BG at an intravenous dose of 120 mg/m2 followed 1 hour later by 40 mg/m2 of BCNU, with cycles repeated at 6-week intervals. RESULTS: Eighteen patients were treated (15 with glioblastoma multiforme, two with anaplastic astrocytoma, and one with malignant glioma). None of the 18 patients demonstrated a partial or complete response. Two patients exhibited stable disease for 12 weeks before their tumors progressed. Three patients demonstrated stable disease for 6, 12, and 18 weeks before discontinuing therapy because of hematopoietic toxicity. Twelve patients experienced reversible ≥ grade 3 hematopoietic toxicity. There was no difference in half-lives (0.56 ± 0.21 hour v 0.54 ± 0.20 hour) or area under the curve values (4.8 ± 1.7 μg/mL/h v 5.0 ± 1.3 μg/mL/h) of O6-BG for patients receiving phenytoin and those not treated with this drug. CONCLUSION: These results indicate that O6-BG plus BCNU at the dose schedule used in this trial is unsuccessful in producing tumor regression in patients with nitrosourea-resistant malignant glioma, although stable disease was seen in five patients for 6, 12, 12, 12, and 18 weeks. Future use of this approach will require strategies to minimize dose-limiting toxicity of BCNU such as regional delivery or hematopoietic stem-cell protection.