Most currently evaluated macromolecular contrast agents for magnetic resonance imaging (MRI) are not biodegradable. The goal of this study is to synthesize and characterize poly(l-glutamic acid) (PG) gadolinium chelates as biodegradable blood-pool MRI contrast agents. Two PG chelates of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) were synthesized through the use of difunctional and monofunctional DTPA precursors. The conjugates were characterized with regard to molecular weight and molecular weight distribution, gadolinium content, relaxivity, and degradability. Distributions of the polymeric MRI contrast agents in various organs were determined by intravenous injection of (111)In-labeled polymers into mice bearing murine breast tumors. MRI scans were performed at 1.5 T in mice after bolus injection of the polymeric chelates. PG-Hex-DTPA-Gd, obtained from aminohexyl-substituted PG and DTPA-dianhydride, was partially cross-linked and was undegradable in the presence of cathepsin B. On the other hand, PG-Bz-DTPA-Gd synthesized directly from PG and monofunctional p-aminobenzyl-DTPA(acetic acid-tert-butyl ester) was a linear polymer and was degradable. The relaxivities of the polymers at 1.5 T were 3-8 times as great as that of Gd-DTPA. Both polymers had high blood concentrations and were primarily accumulated in the kidney. However, PG-Bz-DTPA-Gd was gradually cleared from the body and had significantly less retention in the blood, the spleen, and the kidney. MRI with PG-Bz-DTPA-Gd in mice showed enhanced vascular contrast at up to 2 h after the contrast agent injection. The ability of PG-Bz-DTPA-Gd to be degraded and cleared from the body makes it a favorable macromolecular MRI contrast agent.

Neurofibromatosis 1 is associated with reading disabilities, but few associations between neuroanatomic abnormalities and reading problems have been found. We examined the neuronal bases for phonologic processing, a core component of learning to read, in 15 individuals with neurofibromatosis 1 and 15 controls using functional magnetic resonance imaging (MRI). Our results revealed differential use of inferior and dorsolateral prefrontal cortical areas relative to posterior (temporal, parietal, and occipital) cortices for participants with neurofibromatosis 1 compared with controls during phonologic (rhyme) decisions. In addition, similar to previous brain imaging studies of reading deficits in the general population, poorer performance on one of the phonologic decision tasks was associated with increased signal change in the right superior temporal gyrus for the neurofibromatosis 1 group. Behavioral performance on the functional MRI tasks was related to academic reading measures for the neurofibromatosis 1 group. The differential patterns of functional connectivity observed here lend support to previous morphologic studies that suggested inferior frontal and superior temporal areas to be important mediators of reading and language development in neurofibromatosis 1. ( J Child Neurol 2003;18:731—740).

Neurofibromatosis, type I (NF-I) is associated with verbal and nonverbal neuropsychological deficits and neuroanatomical anomalies. Few relationships between CNS abnormalities and cognitive function in this population, however, have been found. Reading disabilities and developmental language impairments in the general population have been associated with particular morphologic features in inferior frontal gyrus (IFG) and Heschl's gyrus (HG). We compared the morphology of these regions in children with NF-I and controls. Verbal skills in NF-I were related to IFG morphology, such that individuals with NF-I who showed "typical" gyral patterns in the right hemisphere performed worse across language measures than those showing an extra "atypical" gyrus. A doubling of HG in the left and right hemispheres was also significantly associated with performance on several neuropsychological measures. This is the first study to link regional gyral morphology with language function in NF-I. A possible molecular basis for the observed relationships is discussed.

In a recent study, [Hippocampus 11 (2001) 361] demonstrated that in vivo neuroimaging techniques could be used to accurately quantify the extent of neuronal damage after ibotenic acid injections in non-human primates. The present study was undertaken to replicate these findings and to further estimate whether the concentration of ibotenic acid used (10–15 mg/ml) to produce the neuronal loss did not affect the fibers coursing within or around the targeted brain area. Magnetic resonance (MR) images (T1-weighted and FLAIR) were acquired in three monkeys before and after they received neurotoxic lesions of the hippocampal formation. The postsurgical FLAIR images were taken 7–10 days after surgery to visualize the hyperintense signals produced by increased edema at the injection sites. One year post-surgically, T1-weighted images were acquired and compared with T1-weighted images obtained pre-surgery to estimate reduction in hippocampal volume resulting from neuronal loss. Estimated neuronal loss was then compared with actual cell loss found during histological evaluation of brain tissue. Both neuroimaging techniques accurately estimated the extent of hippocampal damage and damage to surrounding structures. In addition, the concentration of ibotenic acid (10 mg/ml) used in the present study did not appear to have significantly damaged or de-myelinated fibers coursing through or around the hippocampal formation. Together with the previous results of [Hippocampus 11 (2001) 361], the present data strongly demonstrate that in vivo neuroimaging techniques provide powerful tools to estimate reliably and rapidly the extent and localization of brain lesions in non-human primates.

Clinical diagnosis of attention-deficit hyperactivity disorder (ADHD) is based on evaluation of behavioral functioning in three domains: inattentiveness, hyperactivity, and impulsivity. Caudate and frontal lobe function figures prominently in several neuroanatomic models of attentional functioning. Studies comparing children with and without ADHD have found differences in the size and symmetry of the caudate nuclei. Using multiple regression, we tested the hypothesis that caudate volume symmetry (log left minus log right caudate volume) measured from serial sagittal magnetic resonance images in a sample of nonreferred children (12 girls/15 boys, 7.0 to 16.6 years, 81 to 129 IQ) would predict the cumulative severity of parent-reported ADHD diagnostic behaviors beyond variance predicted by age, sex, and level of internalizing problems as measured by the Child Behavior Checklist. No child had been previously diagnosed with ADHD, although one child was found to meet diagnostic criteria based on the rating scale used for the study. The degree of caudate asymmetry significantly predicted cumulative severity ratings of inattentive behaviors (P = .015), uniquely accounting for 17.1% of the variance in inattention symptomatology over demographic variables and internalizing problems, which collectively predicted 28.9% of the variance. Caudate asymmetry uniquely accounted for only 4.3% of the variance in cumulative severity ratings of hyperactive/impulsive symptomatology over demographic variables and internalizing problems that collectively predicted 21.2% of the variance. A greater degree of right to left caudate volume asymmetry predicted subclinical inattentive behaviors in a sample of nonreferred children. This finding is congruent with neuroanatomic models of attention emphasizing lateralized alteration in prefrontal/striatal systems. The results support the view that clinical ADHD is the extreme of a behavioral continuum that extends into the normal population. (J Child Neurol 2002;17:877—884).

Functional MRI (fMRI), in a broad sense, has many applications in oncology. In terms of functional task activation imaging, common applications are in image-guided surgical resections of lesions, and applications to non-surgical approaches, such as stereotactic radiation therapy, are currently being evaluated. In terms of functional imaging assessment of the microvascular environment, applications include improved non-invasive characterization of lesions and the ability to quantitatively assess the effects of novel therapeutic regimens on lesions and surrounding normal tissues. Other functional MR applications, such as MR spectroscopy and diffusion imaging techniques, also have found applications in oncology. In this symposium session, current clinical and translational research applications of fMRI in oncology will be briefly reviewed.

The right cerebral hemisphere of 24 rhesus monkeys scheduled for necropsy at the completion of another project were studied histopathologically 1–30 days after a single dose of 60 Co‐irradiation. Histopathologically, inflammation and gliosis consistently occurred at specific time points but varied in severity between individuals. Multifocal hemorrhage, edema, and an acute neutrophilic inflammatory response were observed initially whereas perivascular accumulations of lymphocytes were observed in specimens at the end of the study. Microglia/macrophages were most prominent during the first week after irradiation, whereas astrocytes were reactive throughout the observation period. The early clinical manifestations of the central nervous system (CNS), because of brain irradiation in humans, correspond temporally with acute vascular responses, acute and subacute inflammatory cell responses, and subacute demyelination and reactive astrocytic and microglial responses observed in the rhesus monkey. Initial responses of the CNS to gamma‐irradiation may have potential implications for the development of radiation‐induced late injury of the CNS.

Objective: To determine characteristics of brain morphology in children and adolescents with neurofibromatosis type 1 and relate these characteristics to neuropsychological functioning. Background: Neurofibromatosis type 1 is associated with numerous CNS abnormalities and cognitive impairment. Abnormal high signal intensity visible on brain MRI, brain tumors, and macrocephaly are common. Research into links between neuroanatomic and cognitive features has been inconclusive. Methods: Fifty-two children and adolescents with neurofibromatosis type 1 were compared with 19 control subjects on several quantitative neuroanatomic and neuropsychological measures. Results: Total brain volume, especially gray matter, was significantly greater for neurofibromatosis type 1 subjects than the control subjects. Group differences in the ratio of gray matter to white matter were more prominent in younger than in older subjects. Volume of gray matter in the subjects with neurofibromatosis type 1 was related to their degree of learning disability. Corpus callosum size was significantly larger for subjects in the neurofibromatosis type 1 group, and diminished performance on measures of academic achievement and visual–spatial and motor skills were associated with greater regional corpus callosum size. Conclusions: Neuroanatomic morphology and the developmental pattern of gray matter and white matter in subjects with neurofibromatosis type 1 differed from in control subjects. Some of these differences are related to the neuropsychological status of the neurofibromatosis type 1 group. We propose that delayed developmental apoptosis results in macrocephaly and a delay in the development of appropriate neuronal connections in children with neurofibromatosis type 1. We further propose that these morphologic delays are related to the cognitive profile of neurofibromatosis type 1.

Our purpose was to determine whether triple-dose delayed contrast-enhanced images would improve lesion detection in patients with symptomatic human immunodeficiency virus (HIV) infection. We reviewed 33 MRI studies on 29 patients. Single-dose immediate T 1-weighted spin-echo (1x-T 1) images were compared with delayed triple-dose images (D3x-T 1). Two neuroradiologists decided which technique showed more lesions, increased lesion conspicuity and/or altered the radiologic diagnosis. The D3x-T 1 technique improved lesion detection in 14 of 29 patients (48 %). In two patients (7 %), the improvement changed the radiologic diagnosis by showing new meningeal lesions.

Neurofibromatosis-1 is a common autosomal-dominant genetic disorder associated with numerous physical anomalies and an increased incidence of attention-deficit hyperactivity disorder (ADHD). Studies of children with idiopathic ADHD have suggested a link between corpus callosum size and symptom severity. This study examines the contribution of corpus callosum morphology to symptoms of ADHD in children with neurofibromatosis. Eighteen control subjects and 36 children with neurofibromatosis underwent magnetic resonance imaging of the brain. Twelve subjects with neurofibromatosis had evidence of ADHD and 24 did not. Subjects with neurofibromatosis had significantly larger total corpus callosum area and significantly larger regional measurements in three of seven areas. However, there were no differences between the neurofibromatosis alone and neurofibromatosis plus ADHD groups. Increased severity of attention problems was associated with smaller total callosal areas. These results suggest that some features of ADHD in children with neurofibromatosis could be linked to quantifiable differences in brain morphology, but the nature of the genetic mutation in neurofibromatosis suggests that neurochemical effects also could be important. (J Child Neurol 2000;15:90-96).

We assessed the correlation between dynamic MRI results and clinical outcomes in patients with malignant gliomas. Rapid serial MRIs were obtained after bolus injection of gadolinium that resulted in an initial fast uptake followed by a slow uptake of contrast. The maximum rate of uptake and delayed rate of uptake were correlated with survival and prognostic covariates such as age and histology. In 121 subjects, higher maximum uptake rates, 3.6 signal intensity units per second or greater, were associated with shorter survival (p = 0.0066). The correlation of delayed rate of uptake with survival was less significant. After adjusting for age, histology, and Karnofsky performance score, the maximum rate of uptake remained more significantly correlated with survival than the delayed rate of uptake. Thirty-one patients had surgery within 1 month of dynamic MRI, and those with glioblastoma multiforme or anaplastic gliomas had higher maximum rates of uptake than those with pure necrosis or mixed tumor and necrosis (p = 0.022). No correlation between delayed rate of uptake and histology was seen in this group of patients. Our results suggest that the maximum rate of uptake in dynamic MRI can be a prognostic measure for patients with malignant gliomas. Further prospective study is needed to assess the utility of this technique for evaluating brain tumors.

The purpose of the study reported here was to document the ability of magnetic resonance imaging to depict the imaging characteristics of normal structures within the central nervous system of adult rhesus monkeys, The head and the cervical and thoracic parts of the spinal cord of two rhesus monkeys were imaged in a clinical 1.5-T whole-body imager, Specific images were selected, and some notable structures were identified, Results of this study document the usefulness of MRI as an expeditious, noninvasive research and diagnostic imaging technique and illustrates the normal magnetic resonance signal patterns of the brain and spinal cord in rhesus monkeys.

The purpose of this study was to develop a technique for differentiating between recurrent brain tumors and treatment-related changes, such as radiation necrosis, using dynamic MRI. Ninety-five patients with intracranial mass lesions were evaluated using T1-weighted fast spin-echo (FSE) MRI at 1.5 T. Pathologies included treatment-related changes (n = 32), primary tumors (n = 41), metastatic tumors (n = 5), meningiomas (n = 4), and mixed primary/treatment related changes (n = 13), Signal enhancement-time curves were analyzed by fitting to a sigmoidal-exponential function. Maximal enhancement rates were calculated as the first derivative of the fitted curve. Based on the maximal enhancement rates, treatment-related changes could be differentiated from primary tumors, metastatic tumors, and meningiomas at the P < .05 confidence level. Lesions of mixed tumor and treatment-related change had intermediate values. Dynamic MRI can be used to differentiate treatment-related changes from primary tumors in previously treated patient populations based on maximal enhancement rates,Individual case studies demonstrate the clinical significance of these findings.

The authors retrospectively evaluated magnetic resonance images of the abdomen obtained in 52 consecutive patients. All cases included fast spin-echo (FSE) T2-weighted images acquired with a frequency-selective fat saturation technique. All imaging was performed with a 1.5-T unit. In 42 patients (81%), fat was not suppressed in the right anterior diaphragmatic region on the T2-weighted FSE images with fat suppression. In 11 (26%) of these 42 patients, subcutaneous fat adjacent to the unsuppressed anterior diaphragmatic fat was well suppressed. Hence, the fat in the diaphragmatic region mimicked fluid or peritoneal implants. The cause of the artifact appears to be the juxtaposition of liver, fat, and lung parenchymal air within a small anatomic space, creating a localized inhomogeneity of the magnetic field and susceptibility effects. Radiologists should be aware of this phenomenon to prevent confusion of an artifact with fluid or neoplasms.