Dynamic contrast-enhanced perfusion processing for neuroradiologists: model-dependent analysis may not be necessary for determining recurrent high-grade glioma versus treatment effect.

BACKGROUND AND PURPOSE: Dynamic contrast-enhanced perfusion MR imaging has proved useful in determining whether a contrast-enhancing lesion is secondary to recurrent glial tumor or is treatment-related. In this article, we explore the best method for dynamic contrast-enhanced data analysis. MATERIALS AND METHODS: We retrospectively reviewed 24 patients who met the following conditions: 1) had at least an initial treatment of a glioma, 2) underwent a half-dose contrast agent (0.05-mmol/kg) diagnostic-quality dynamic contrast-enhanced perfusion study for an enhancing lesion, and 3) had a diagnosis by pathology within 30 days of imaging. The dynamic contrast-enhanced data were processed by using model-dependent analysis (nordicICE) using a 2-compartment model and model-independent signal intensity with time. Multiple methods of determining the vascular input function and numerous perfusion parameters were tested in comparison with a pathologic diagnosis. RESULTS: The best accuracy (88%) with good correlation compared with pathology (P = .005) was obtained by using a novel, model-independent signal-intensity measurement derived from a brief integration beginning after the initial washout and by using the vascular input function from the superior sagittal sinus for normalization. Modeled parameters, such as mean endothelial transfer constant > 0.05 minutes(-1), correlated (P = .002) but did not reach a diagnostic accuracy equivalent to the model-independent parameter. CONCLUSIONS: A novel model-independent dynamic contrast-enhanced analysis method showed diagnostic equivalency to more complex model-dependent methods. Having a brief integration after the first pass of contrast may diminish the effects of partial volume macroscopic vessels and slow progressive enhancement characteristic of necrosis. The simple modeling is technique- and observer-dependent but is less time-consuming.

Computed tomography (CT) in the diagnosis of intracranial abscesses. Brain abscess, subdural empyema, and epidural empyema.

Nine cases of brain abscess, five of subdural empyema, and one of epidural empyema with associated subdural empyema were identified using computed tomography (CT). Smal and multiple abscesses as well as unilateral, bilateral, and parafalcine empyemas were detected. These lesions were demonstrated rapidly and accurately, even in areas that are demonstrated poorly by other diagnostic techniques. No false-negative studies were found in cases of brain abscess or subdural empyema. However, since the appearance of brain abscesses of CT scans is similar to that of neoplastic and vascular lesions, false-positive reports of brain abscess were encountered.

Lateral pontine tegmental hemorrhage presenting as isolated trigeminal sensory neuropathy.

A 45-year-old man awoke with numbness and paresthesias on the right side of his face, scalp, ear, and tongue. CT and MRI demonstrated a focal hemorrhage in the dorsolateral right pontine tegmentum. Cerebral angiography was negative for vascular malformation or aneurysm. CT performed 1 month later showed complete resolution of the pontine hematoma, with residual minimal lateral pontine atrophy.

Computed tomography in Herpes simplex encephalitis.

Eight patients with Herpes simplex encephalitis had computed cranial tomography (CT). In every case, areas of decreased attenuation were found in the temporal lobe(s); these areas extended to the insular cortex and often to the frontal or parietal lobes. This change developed between the third and the eleventh day of illness. It was present, sometimes only in retrospect, in patients who were alert as well as patients who were comatose. Compared to the isotopic brain scan, electroencephalogram, and cerebral angiogram, CT demonstrates changes that are indicative of H simplex early enough in the course of the illness to be therapeutically useful.

Verbal asomatognosia.

Verbal asomatognosia is a form of neglect in which a patient denies ownership of a limb contralateral to a brain lesion. To establish the neuroanatomic substrate of this syndrome, we analyzed the CTs of 12 right-hemisphere stroke patients with neglect and verbal asomatognosia and 4 patients with neglect but without asomatognosia. Of 16 cortical and subcortical brain regions analyzed, supramarginal gyrus and its subcortical connections within posterior corona radiata were most consistently involved in the asomatognosia cases. One or both of these regions were spared in all cases of neglect without asomatognosia. Our data confirm Nielsen's localization of asomatognosia to the right supramarginal gyrus and thalamoparietal peduncle. Converging lines of evidence from experiments in humans and monkeys suggest that damage to area PF may be necessary for the production of personal neglect of a limb.

Brain volume in children with neurofibromatosis type 1: relation to neuropsychological status.

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.

Luetic meningitis with gumma: clinical, radiographic, and neuropathologic features.

A 28-year-old man had headache and unilateral third-nerve palsy as the presenting features of acute syphilitic meningitis, accompanied by an asymptomatic cerebral gamma.

Correlation between dynamic MRI and outcome in patients with malignant gliomas.

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.

Phase II study of accelerated fractionation radiation therapy with carboplatin followed by vincristine chemotherapy for the treatment of glioblastoma multiforme.

PURPOSE: To conduct a Phase II one-arm study to evaluate the long-term efficacy and safety of accelerated fractionated radiotherapy combined with intravenous carboplatin for patients with previously untreated glioblastoma multiforme tumors. METHODS AND MATERIALS: Between 1988 and 1992, 83 patients received 1.9-2.0 Gy radiation three times a day with 2-h infusions of 33 mg/m2 carboplatin for two 5-day cycles separated by 2 weeks; following radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until tumor progressed. RESULTS: Eighty-three patients were evaluable for analysis. Seventy-four of the 83 patients (89%) received one or more courses of PCV; their median survival was 55 weeks. Total resection was performed in 20% (15 of 74), subtotal resection in 69% (51 of 74), and biopsy in 11% (8 of 74); reoperation (total or subtotal resection) was performed in 28 patients (37%). Survival was worst for those > or = 61 year old (median 35 weeks). Fits of the Cox proportional hazards regression model showed covariates individually predictive of improved survival were younger age (p < 0.01), smaller log of radiation volume (p = 0.008), total or subtotal resection vs. biopsy (p = 0.056), and higher Karnofsky performance status (p = 0.055). A multivariate analysis showed that age (p = 0.013) and extent of initial surgery (p = 0.003) together were predictive of a better survival with no other variables providing additional significance. Only 8.4% (7 of 83) of patients had clinically documented therapy-associated neurotoxicity ("radiation necrosis"). CONCLUSION: When comparable selection criteria were applied, the survival in this study is similar to the results currently attainable with other chemoradiation approaches. The relative safety of accelerated fractionated radiotherapy, as used in this study with carboplatin, enables concomitant full-dose administration of chemotherapy or radiosensitizing agents in glioblastoma multiforme patients.

Phase II study of accelerated fractionation radiation therapy with carboplatin followed by PCV chemotherapy for the treatment of anaplastic gliomas.

PURPOSE: To conduct a Phase II one-arm study to evaluate the long-term efficacy and safety of accelerated fractionated radiotherapy combined with i.v. carboplatin for patients with previously untreated anaplastic gliomas. METHODS AND MATERIALS: Between 1988 and 1992, 90 patients received 1.9-2.0-Gy radiation 3 times a day with 2-h infusions of 33 g/m(2) carboplatin for two 5-day cycles separated by 2 weeks. After radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until the tumor progressed. RESULTS: Ninety patients were evaluable for analysis. Histologically, 69 had anaplastic astrocytoma; 14, anaplastic oligoastrocytoma; and 7, anaplastic oligodendroglioma. Gross total resection was performed in 20 (22%), subtotal resection in 45 (50%), and biopsy in 25 (28%); reoperation (total or subtotal resection) was performed in 50 (56%) patients. A multivariate analysis showed that a younger age (p = 0.026), Karnofsky performance score (KPS; p = 0.009), and brain necrosis (p = 0.0002) were predictive of a better survival. Results from analysis of extent of surgery (biopsy, subtotal resection, gross total resection) approached significance (p = 0.058). Radiation dose, irradiated tumor volume, and techniques used (boost and fields) were not significant variables. The median survival (MS) of all anaplastic glioma patients was 28.1 months; for anaplastic astrocytoma patients, MS was 28.7 months and 40.8 months for the combined anaplastic oligodendroglioma/oligoastrocytoma patients. Long-term survival occurred in 25% of anaplastic glioma patients who were alive 8.6 years after treatment was initiated. Treatment-induced necrosis was documented by surgery or autopsy in 19 (21%) patients; 21 (23%) had a mixed pattern of necrosis and tumor; and an additional 13 (14%) patients who did not have surgical or autopsy demonstration of predominant radiation necrosis had magnetic resonance imaging (MRI) evidence of radiation necrosis. Serious clinical neurologic deterioration and/or dementia requiring full-time caregiver attention were observed in 9 (10%) patients. CONCLUSION: When comparable selection criteria are applied, the rate of MS in this study is inferior to results attainable with current radiation and chemotherapy approaches, although the rates of long-term survival are comparable. Theoretically, patients failing therapy and dying earlier than anticipated may be because of excessive central nervous system (CNS) toxicity resulting from the combination of accelerated fractionated irradiation, intensive carboplatin chemotherapy before each radiation fraction, and postirradiation PCV chemotherapy. On the other hand, patients with treatment-induced necrosis survived significantly longer than patients who did not demonstrate MRI or histologic evidence of necrosis (MS, 106 months vs. 18-33 months).

The clinical application of radiopharmaceuticals.

This article highlights the choices and the arguments in the selection of appropriate contrast materials in radiological examinations--nonionic versus ionic contrast material--and aims to assist the physician in decision-making. Various authors have raised questions concerning the proposed advantages of nonionic contrast material. However, studies in low risk patients have shown more complications with the use of ionic contrast than nonionic contrast materials; this is the important group of patients since in high risk patients nonionics are used almost exclusively. The important factor that increases the controversy is cost, which is significant since nonionic agents cost 10 to 15 times more than ionic agents in the USA. Thus, cost-benefit considerations are important because price sensitivity and cost may determine fund availability for equipment or materials that also may be necessary or important in improving patient care. In magnetic resonance imaging (MRI), as in computed tomography (CT), the use of contrast material has improved diagnostic accuracy and the ability to reveal lesions not otherwise easily detected in brain and spinal cord imaging. These include separating scan from disc, meningitis, meningeal spread of tumour, tumour seeding, small metastases, intracanalicular tumours, separating major mass from oedema, determining bulk tumour size and ability to demonstrate blood vessels so dynamic circulatory changes may be revealed.

The effect of erythromycin on theophylline pharmacokinetics at steady state.

We compared steady-state theophylline pharmacokinetics in 13 healthy adults before and immediately after erythromycin therapy. All subjects received a five-day course of oral aminophylline 3 mg/kg every six hours prior to and during a five-day course of oral erythromycin stearate (1 g daily). Each subject acted as his own control. Multiple serum samples were collected over ten hours following the last dose of aminophylline during both the control and experimental phases of the study. Erythromycin did not significantly affect theophylline clearance (P greater than 0.70), elimination (P greater than 0.75), or volume of distribution (P greater than 0.30). We found no evidence of a pharmacokinetic interaction between theophylline and erythromycin at steady state. Worsening pulmonary function may be responsible for altered theophylline pharmacokinetics in patients coincidentally receiving erythromycin.

Magnetic resonance imaging in patients with central nervous system pathology: a comparison of OptiMARK (Gd-DTPA-BMEA) and Magnevist (Gd-DTPA).

RATIONALE AND OBJECTIVES: The objective of the two pivotal phase 3 studies was to evaluate the safety and efficacy of OptiMARK (Gd-DTPA-bis(methoxyethylamide) [Gd-DTPA-BMEA]) compared with Magnevist (Gd-DTPA) in magnetic resonance imaging of the central nervous system. METHODS: Two multicenter, randomized, double-blind, parallel group studies were conducted in 395 patients with known or suspected central nervous system pathology. Subjects were randomized to receive a single 0.1 mmol/kg intravenous injection of either Gd-DTPA-BMEA or Gd-DTPA. The safety of Gd-DTPA-BMEA and Gd-DTPA was monitored for up to 72 hours after study drug administration. Precontrast and postcontrast administration magnetic resonance scans were acquired using identical imaging planes and techniques. RESULTS: No deaths or unexpected adverse events were reported in either group. A comparison of adverse events by intensity and relation demonstrated no statistically significant differences between the two groups. Gd-DTPA-BMEA and Gd-DTPA were equivalent with respect to confidence in diagnosis, conspicuity, and border delineation. CONCLUSIONS: Gd-DTPA-BMEA and Gd-DTPA demonstrated comparable efficacy profiles, and the safety profiles were considered similar.

Effect of food on the bioavailability and pattern of release of a sustained-release theophylline tablet.

The effect of food on the bioavailability, time to peak level, and pattern of release of a sustained-release theophylline preparation was examined in six normal volunteers. The average bioavailability for the 100- and 300-mg tablets was 98 +/- 0.03% (S.E.M.). This is consistent with previously published data. Food decreased measured theophylline concentration during the first 4 hours for the 100-mg tablets and at the fourth-hour sample following the 300-mg tablets. The decreased rate of absorption resulted in a shift of the absorption curve to the right with a delay in the time to peak level. Peak serum concentrations for tablets given with a meal occurred 6 hours after the 100-mg tablets and 8 hours after the 300-mg tablets, as opposed to 4 and 6 hours, respectively, for tablets in the fasting state. The release pattern of the theophylline preparation approximated zero-order kinetics for all fasting and food treatments.

Falx and interhemispheric fissure on axial CT: II. Recognition and differentiation of interhemispheric subarachnoid and subdural hemorrhage.

Interhemispheric hyperdensity or unenhanced computed tomography was originally considered a sign of subarachnoid hemorrhage, the "falx sign." It has since been identified as a normal feature and has also been seen with interhemispheric subdural hemorrhage. To determine the differential features of interhemispheric hemorrhage, 50 patients with subarachnoid hemorrhage and 32 patients with interhemispheric subdural hematomas were reviewed. Subarachnoid hemorrhage produced anterior interhemispheric hyperdensity only, with a zigzag contour and extension from the calvarium to the rostrum of the corpus callosum. Interhemispheric subdural hematomas produce unilateral crescentic hyperdensities that are largest in the posterior superior part of the fissure, behind and above the splenium of the corpus callosum. Interhemispheric hyperdensity in children is more complex. Because the anterior part of the fissure is narrow in younger patients, subarachnoid hemorrhage may go undetected. Likewise, interhemispheric subdural hematomas in children are smaller and more difficult to recognize. They produce asymmetric thickening of the falx shadow with extension over the tentorium. They are, however, of great significance since they are generally seen in abused patients and carry a poor prognosis.

The value of unenhanced scans in differentiating lesions producing ring enhancement.

Ring enhancement with contrast material is a nonspecific computed tomographic finding seen in a variety of lesions, including benign and malignant neoplasms, inflammation, infarction, and hematoma. This lack of specificity is especially troublesome in the differentiation of self-limiting disorders (infarction and hematoma) from progressive processes (tumor or abscess) potentially requiring surgical treatment. To determine whether more specific diagnoses were possible, 115 cases with ring lesions were retrospectively evaluated for the usefulness of precontrast scan features. The presence or absence of a complete ring proved useful. A complete ring on unenhanced scans effectively excluded self-limiting processes; it was seen in none of 18 infarcts or 11 hematomas. A complete ring on unenhanced scans occurred in 37 of 65 neoplasms, and was more common in metastatic disease (2:1) than in gliomas. A complete ring on unenhanced computed tomography was also seen in four of 15 pyogenic abscesses.

Axial CT recognition of anteroposterior displacement of fourth ventricle.

The recognition of anterior or posterior displacement of the fourth ventricle on axial computed tomography (CT) has proven to be difficult because the apparent position of this structure is variable and dependent on scanning angle. In most cases direct visualization of a lesion and its relationship to normal anatomic structures allows for the correct assessment. However, in some instances it would be advantageous for lesion localization to be able to identify relatively subtle displacements of the fourth ventricle. This is possible on CT by determining the position of this structure relative to Twining's line (the line between the tuberculum sellae and torcula). The position of the fourth ventricle, tuberculum sellae, and torcula relative to an arbitrary fixed point can be established in virtually all cases, and thus the position of the fourth ventricle relative to Twining's line can be determined. In a control group of 100 patients with normal CT examinations, the ratio of the distance from the tuberculum sellae to the center of the fourth ventricle and the distance from the tuberculum sellae to torcula (Twining's line) was between 0.47 and 0.53. In 66% of the cases the ratio was 0.49-0.51. THere were 54 posterior fossa masses evaluated by this technique. Determination of fourth ventricular position by this method proved to be of particular value in recognizing brainstem glioma, and in determining the site of origin of laterally placed posterior fossa masses.

Aortic arch digital arteriography: an alternative technique to digital venous angiography and routine arteriography in the evaluation of cerebrovascular insufficiency.

Digital arch arteriography is a technique in which the cervicocerebral vasculature is studied by injecting small amounts of contrast material (20 ml or less of diatrizoate meglumine 60%) into the aortic arch. It was used as the initial phase of arteriography in 100 patients with cerebrovascular disease. Five to ten series were obtained in various projections to evaluate the cerebrovascular system. Because suboptimal studies may be repeated, only 3% of carotid bifurcations were suboptimally visualized by digital arch arteriography as compared with 17% by film arch angiography. Intracranial vascular pathology was identified less reliably than with selective angiography. Digital arch arteriography yielded excellent studies in cases when digital venous angiography was suboptimal (20%). Digital arch arteriography may be preferable to digital venous angiography as a screening test in patients with significant cardiac or renal dysfunction because of the lower contrast load.

MR of toxic effects of accelerated fractionation radiation therapy and carboplatin chemotherapy for malignant gliomas.

PURPOSE: To present MR findings of parenchymal brain injury after accelerated fractionation radiation therapy combined with carboplatin chemotherapy in the treatment of malignant brain gliomas. METHODS: Eighty-one evaluable subjects in an ongoing treatment protocol for malignant gliomas form the patient base for this report. After surgical resection of tumors, patients underwent a course of accelerated fractionation radiation therapy to a total dose of 60 Gy. Carboplatin was infused intravenously before each radiation treatment. Precontrast and postcontrast MR scans were obtained before treatment and at 4-week intervals afterward and were analyzed retrospectively. RESULTS: Posttreatment MR imaging in 20 of the 81 patients showed development of unusual parenchymal lesions or enlarging masses needing debulking, and these patients underwent second operations. Two groups emerged: those with tumor and necrotic brain (n = 11) and those with necrosis and reactive gliosis but no definitive tumor (n = 9). Enhancing lesions in the tumor-negative group appeared later than those in the tumor-positive group, were often multiple, and were usually located several centimeters away from the tumor resection site or even contralaterally. Common locations were the corpus callosum and corticomedullary junctions. Lesions in the tumor-positive group were more often solitary and located immediately adjacent to the surgical site. Positive and negative results of positron emission tomography with fludeoxyglucose F 18 were obtained in both groups. The incidence of brain necrosis without associated tumor was 11%. CONCLUSIONS: A pattern of unusual enhancing parenchymal brain lesions was seen on MR imaging after accelerated fractionation radiation therapy and concomitant carboplatin chemotherapy. The abnormalities seem more extensive than focal necrotic lesions on enhanced CT or MR imaging after conventional radiation therapy, and they may mimic recurrent tumor.

Magnetic resonance imaging of benign spinal lesions simulating metastasis: role of diffusion-weighted imaging.

In an attempt to avoid unnecessary therapy, this article demonstrates benign vertebral body lesions that mimic metastatic disease in cancer patients with back pain. The magnetic resonance imaging features that aid in differential diagnosis are demonstrated. In addition, the value of diffusion-weighted spinal imaging to further aid in distinguishing benign from malignant disease is described.