June S. Taylor

Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols

We describe a standard set of quantity names and symbols related to the estimation of kinetic parameters from dynamic contrast‐enhanced T1‐weighted magnetic resonance imaging data, using diffusable agents such as gadopentetate dimeglumine (Gd‐DTPA). These include a) the volume transfer constant Ktrans (min−1); b) the volume of extravascular extracellular space (EES) per unit volume of tissue ve (0 < ve < 1); and c) the flux rate constant between EES and plasma kep (min−1). The rate constant is the ratio of the transfer constant to the EES (kep = Ktrans/ve). Under flow‐limited conditions Ktrans equals the blood plasma flow per unit volume of tissue; under permeability‐limited conditions Ktrans equals the permeability surface area product per unit volume of tissue. We relate these quantities to previously published work from our groups; our future publications will refer to these standardized terms, and we propose that these be adopted as international standards. J. Magn. Reson. Imaging 10:223–232, 1999.

Risks of Young Age for Selected Neurocognitive Deficits in Medulloblastoma Are Associated With White Matter Loss

PURPOSE To test the hypothesis that inadequate development of normal-appearing white matter (NAWM) is associated with the relationship between young age at the time of craniospinal irradiation (CRT) and deficient neurocognitive performance in survivors of childhood medulloblastoma. PATIENTS AND METHODS Forty-two patients treated since 1985 participated in this cross-sectional study. All had been treated with CRT with or without chemotherapy and had survived 1 or more years after treatment. Neurocognitive evaluations were conducted with tests of intellect (intelligent quotient; IQ), verbal memory, and sustained attention. Quantitative magnetic resonance imaging, using a hybrid neural network, assessed the volume of NAWM. RESULTS Neurocognitive test results were below normal expectations for age at the time of testing. A young age at CRT was significantly associated with worse performance on all neurocognitive tests except that of verbal memory. An increased time from completion of CRT was significantly associated with worse performance on all neurocognitive tests except that of sustained attention. After statistically controlling for the effects of time from CRT, we examined the association of NAWM with neurocognitive test results. These analyses revealed that NAWM accounted for a significant amount of the association between age at CRT and IQ, factual knowledge, and verbal and nonverbal thinking, but not sustained attention or verbal memory. CONCLUSION The present results suggest that, at least for some cognitive functions, deficient development and/or loss of NAWM after CRT may provide a neuroanatomical substrate for the adverse impact of a young age at the time of CRT.

MR imaging of tumor microcirculation: Promise for the new millenium†

Dynamic contrast‐enhanced magnetic resonance imaging (DCE MRI) is a method of imaging the physiology of the microcirculation. A series of recent clinical studies have shown that DCE MRI can measure and predict tumor response to therapy. Recent advances in MR technology provide the enhanced spatial and temporal resolution that allow the application of this methodology in the management of cancer patients. The September issue of this journal provided a microcirculation section to update readers on this exciting and challenging topic. Evidence is mounting that DCE MRI‐based measures correlate well with tumor angiogenesis. DCE MRI has already been shown in several types of tumors to correlate well with traditional outcome measures, such as histopathologic studies, and with survival. These new measures are sensitive to tumor physiology and to the pharmacokinetics of the contrast agent in individual tumors. Moreover, they can present anatomical images of tumor microcirculation at excellent spatial resolution. Several issues have emerged from recent international workshops that must be addressed to move this methodology into routine clinical practice. First, is complex modeling of DCE MRI really necessary to answer clinical questions reliably? Clinical research has shown that, for tumors such as bone sarcomas, reliable outcome measures of tumor response to chemotherapy can be extracted from DCE MRI by methods ranging from simple measures of enhancement to pharmacokinetic models. However, the use of similar methods to answer a different question—the differentiation of malignant from benign breast tumors—has yielded contradictory results. Thus, no simple, one‐size‐fits‐all‐tumors solution has yet been identified. Second, what is the most rational and reliable data collection procedure for the DCE MRI evaluation? Several groups have addressed population variations in some key variables, such as tumor T10 (T1 prior to contrast administration) and the arterial input function Ca(t) for contrast agent, and how they influence the precision and accuracy of DCE MRI outcomes. However, despite these potential complications, clinical studies in this section show that some tumor types can be assessed by relatively simple dynamic measures and analyses. The clinical scenario and tumor type may well determine the required complexity of the DCE MRI exam procedure and its analysis. Finally, we suggest that a consensus on naming conventions (nomenclature) is needed to facilitate comparison and analysis of the results of studies conducted at different centers. J. Magn. Reson. Imaging 10:903–907, 1999.

The correlation between phase shifts in gradient-echo MR images and regional brain iron concentration☆

The purpose of this study was to investigate the relationship between the magnetic susceptibility of brain tissue and iron concentration. Phase shifts in gradient-echo images (TE = 60 ms) were measured in 21 human subjects, (age 0.7-45 years) and compared with published values of regional brain iron concentration. Phase was correlated with brain iron concentration in putamen (R2 = 0.76), caudate (0.72), motor cortex (0.68), globus pallidus (0.59) (all p < 0.001), and frontal cortex (R2 = 0.19, p = 0.05), but not in white matter (R2 = 0.05,p = 0.34). The slope of the regression (degrees/mg iron/g tissue wet weight) varied over a narrow range from -1.2 in the globus pallidus and frontal cortex to -2.1 in the caudate. These results suggest that magnetic resonance phase reflects iron-induced differences in brain tissue susceptibility in gray matter. The lack of correlation in white matter may reflect important differences between gray and white matter in the cellular distribution and the metabolic functions of iron. Magnetic resonance phase images provide insight into the magnetic state of brain tissue and may prove to be useful in elucidating the relationship between brain iron and tissue relaxation properties.

Neurocognitive deficits in medulloblastoma survivors and white matter loss

Although previous studies have documented a significant risk of intellectual loss after treatment for childhood medulloblastoma (MED), the pathophysiology underlying this process is poorly understood. The purpose of this study was to test the hypotheses that (1) patients treated for MED in childhood have reduced volumes of normal white matter (NWM) related to their treatment with craniospinal irradiation with or without chemotherapy, and (2) deficits in NWM among patients surviving MED can at least partially explain deficits in their intellectual performance. Eighteen pediatric patients previously treated for MED were matched on the basis of age at the time of evaluation to 18 patients previously treated for low‐grade posterior fossa tumors with surgery alone (mean difference, 3.7 months). Evaluations were conducted with age‐appropriate neurocognitive testing and quantitative magnetic resonance imaging by using a novel automated segmentation and classification algorithm constructed from a hybrid neural network. Patients treated for MED had significantly less NWM (p < 0.01) and significantly lower Full‐Scale IQ values than those treated for low‐grade tumors (mean, 82.1 vs 92.9). In addition, NWM had a positive and statistically significant association with Full‐Scale IQ among the patients treated for MED. We conclude that irradiation‐ or chemotherapy‐induced destruction of NWM can at least partially explain intellectual and academic achievement deficits among MED survivors.

Dynamic MR imaging (DEMRI) of microcirculation in bone sarcoma.

If chemotherapy is to be effective against bone sarcoma, the cytotoxic agents must reach all tumor cells in effective quantities. Although many clinical trials include studies of the pharmacokinetics of these agents in blood or cerebrospinal fluid, there have been no accurate or widely applicable methods of determining whether chemotherapeutic agents reach all regions of a solid tumor. This review discusses the use of dynamic contrast‐enhanced magnetic resonance imaging (DEMRI) to assess the microcirculation and interstitium of bone sarcoma. DEMRI studies provide a means of exploring leakage of contrast agent into tumor interstitium (extracellular extravascular spaces [EES]). In clinical observations of numerous series of patients with bone sarcoma, measures of contrast uptake (access) have convincingly demonstrated a relationship with measures and predictions of the tumors response to preoperative chemotherapy. The results of these studies have indicated that greater access at the time of presentation, greater decrease in access during therapy, and low access at the completion of preoperative therapy correspond to better response and longer disease‐free survival. Although questions remain about how these novel dynamic imaging methods can best be used to measure drug access noninvasively, we are optimistic that such measures can be developed to reflect the range of biological variation within and between naturally occurring solid tumors. J. Magn. Reson. Imaging 1999;10:277–285.

CLINICAL VALUE OF PROTON MAGNETIC RESONANCE SPECTROSCOPY FOR DIFFERENTIATING RECURRENT OR RESIDUAL BRAIN TUMOR FROM DELAYED CEREBRAL NECROSIS

PURPOSE Delayed cerebral necrosis (DN) is a significant risk for brain tumor patients treated with high-dose irradiation. Although differentiating DN from tumor progression is an important clinical question, the distinction cannot be made reliably by conventional imaging techniques. We undertook a pilot study to assess the ability of proton magnetic resonance spectroscopy (1H MRS) to differentiate prospectively between DN or recurrent/residual tumor in a series of children treated for primary brain tumors with high-dose irradiation. METHODS AND MATERIALS Twelve children (ages 3-16 years), who had clinical and MR imaging (MRI) changes that suggested a diagnosis of either DN or progressive/recurrent brain tumor, underwent localized 1H MRS prior to planned biopsy, resection, or other confirmatory histological procedure. Prospective 1H MRS interpretations were based on comparison of spectral peak patterns and quantitative peak area values from normalized spectra: a marked depression of the intracellular metabolite peaks from choline, creatine, and N-acetyl compounds was hypothesized to indicate DN, and median-to-high choline with easily visible creatine metabolite peaks was labeled progressive/recurrent tumor. Subsequent histological studies identified the brain lesion as DN or recurrent/residual tumor. RESULTS The patient series included five cases of DN and seven recurrent/residual tumor cases, based on histology. The MRS criteria prospectively identified five out of seven patients with active tumor, and four out of five patients with histologically proven DN correctly. Discriminant analysis suggested that the primary diagnostic information for differentiating DN from tumor lay in the normalized MRS peak areas for choline and creatine compounds. CONCLUSIONS Magnetic resonance spectroscopy shows promising sensitivity and selectivity for differentiating DN from recurrent/progressive brain tumor. A novel diagnostic index based on peak areas for choline and creatine compounds may provide a simple discriminant for differentiating DN from recurrent or residual primary brain tumors.

Evolution from empirical dynamic contrast-enhanced magnetic resonance imaging to pharmacokinetic MRI.

For chemotherapy to be effective against cancers which grow as solid tumors, agents must reach all tumor cells in effective quantities. Although many clinical trials include studies of the pharmacokinetics of the agents in body fluids such as blood or cerebrospinal fluid (CSF), there is presently no widely applicable way to determine access of chemotherapeutic agents to all regions of a solid tumor in an individual patient. This review discusses a relatively new methodology in MR imaging - dynamic contrast-enhanced imaging for exploring tumor microcirculation and drug access by imaging the uptake, or leakage, of contrast agent into tumor interstitial (extracellular and extravascular) space. The aims and methods of dynamic contrast-enhanced MRI evaluations to measure contrast uptake are distinguished from dynamic contrast-enhanced MRI to measure blood volume or flow, by MR imaging of the first-pass effects of a contrast bolus. Measures of contrast uptake by dynamic MRI have demonstrated a convincing ability to aid in diagnosing the presence of viable tumor and to measure response for a range of human tumors. This body of clinical results will be summarized. While questions remain to be answered about how to extract non-invasive pharmacokinetic measures of drug access from these novel dynamic imaging methods, we are optimistic that these methods can provide important new clinical measures that reflect the range of biological variation within and between naturally-occurring solid tumors.

Visual evoked potentials in children with neurofibromatosis type 1

The purposes of this investigation were to determine: (a) if visual evoked potential (VEP) abnormalities could be identified in children with neurofibromatosis type 1 (NF1) with no evidence of optic pathway or brain neoplasias on MRI; and (b) if VEP abnormalities could be explained by the presence of hyperintense T2-weighted foci on MRI testing, known as unidentified bright objects (UBOs). To answer these questions, VEPs were recorded from 16 children with NF1 and compared to 13 normal subjects in the same age range tested with the same protocol. Pattern-reversal VEPs were recorded at four stimulus sizes both monocularly and binocularly, the latter to hemi-field stimuli. Flash VEPs were recorded in dark- and light-adapted conditions. VEP measurements and MRI readings for UBOs were conducted in a masked fashion. Ten of the 16 children with NF1 had abnormal VEPs to at least one of the four types of stimuli. Abnormalities included delayed responses (n=6), absent flash VEP P2 component (n=3), or both (n=1). Abnormalities of the P2 component of the dark-adapted flash VEP were the most common finding (n=7), although no single testing strategy was able to identify all children with abnormal VEPs. UBOs were present in all children, demonstrating that their presence does not fully account for VEP abnormalities in children with NF1. This study also demonstrates that VEP abnormalities are present also in the absence of neoplasias of the optic pathways or of the brain. Our results are suggestive of a primary abnormality of visual processing in children with NF1.