Brain magnetic resonance diffusion abnormalities in Creutzfeldt-Jakob disease.

BACKGROUND: Magnetic resonance imaging of the brain has been of limited usefulness in the diagnosis of Creutzfeldt-Jakob disease. Abnormalities on T2-weighted images have been described, but these are neither highly sensitive nor specific. OBJECTIVE: To determine whether diffusion-weighted magnetic resonance images might be useful in the evaluation of Creutzfeldt-Jakob disease. CASE PRESENTATION: A 61-year-old woman with rapidly progressive dementia was referred for cranial magnetic resonance imaging. Diffusion-weighted images were obtained as part of the examination. Brain biopsy confirmed the diagnosis of Creutzfeldt-Jakob disease histologically. FINDINGS AND CONCLUSIONS: The diffusion-weighted magnetic resonance brain images demonstrated bilaterally symmetrical marked increase in signal intensity in the caudate nuclei, putamina, thalami, cingulate gyri, and right inferior frontal cortex. The apparent diffusion coefficient map showed abnormally low diffusion in these regions (as low as 40% of normal in the caudate head). This suggests that there is restricted diffusion in these regions. The T2-weighted images demonstrated slightly increased signal bilaterally in the caudate nuclei and putamina. These findings indicate that diffusion magnetic resonance imaging might be a sensitive means of imaging the abnormalities seen in Creutzfeldt-Jakob disease.

Clinical evaluation of stenosis of the carotid bifurcation with magnetic resonance angiographic techniques.

We evaluated the images of 60 carotid artery bifurcations in 31 patients suspected to have carotid artery disease who underwent invasive carotid angiography and combined two-dimensional, phase-sensitive and a gradient-echo magnetic resonance angiography. The phase scans consisted of seven serial projections that were obtained at 20 degrees intervals (11.0 minutes) around the carotid bifurcation; the gradient-echo (GRASS) scans were composed of 11 axial images (2.4 minutes) acquired through the bifurcation. The two magnetic resonance angiographic techniques yielded complementary pieces of information and were used together to compare magnetic resonance angiography with invasive angiography. Comparison of magnetic resonance and invasive angiograms of the 60 carotid arteries shows that the sensitivity (86%) and specificity (92%) of the magnetic resonance angiographic techniques we used to diagnose clinically significant carotid stenosis approach but do not reach those of invasive angiography.

Clinical-pathologic correlation in Huntington's disease: a neuropsychological and computed tomography study.

To examine the premise that cognitive impairment in Huntington's disease (HD) is related to striatal degeneration, we determined those cognitive deficits most closely associated with linear CT indices of brain atrophy in HD. We systematically evaluated 60 drug-free HD patients who were judged to be in stages I (n = 34) or II (n = 26) of illness. All subjects underwent comprehensive neuropsychological assessment covering a broad spectrum of cognitive operations and standardized head CT imaging for determination of frontal horn (FH), intercaudate (CC), and outer-table (OT) distances. We grouped the cognitive test results, based on a principal-component factor analysis, to form factors 1 (complex psychomotor), 2 (verbal memory), 3 (visuospatial), and 4 (general knowledge). Factors 1 and 3 sharply discriminated between subjects in stages I and II of illness. Factors 1, 2, and 3 correlated strongly with CC/OT, an index of caudate atrophy, whereas only factor 2 correlated with FH/OT, an index of frontal atrophy. These data demonstrate that cognitive impairment is a clear-cut characteristic of early HD that is linked closely to the extent of caudate atrophy as measured by CT.

A prospective evaluation of cognitive decline in early Huntington's disease: functional and radiographic correlates.

We examined prospectively the relationship between progressive disability in Huntington's disease (HD) and concomitant alterations in neuropsychological functioning and brain imaging indices in a cohort of 60 patients who were enrolled and followed for 30 to 42 months in a controlled clinical trial. Standardized measures of functional capacity and neuropsychological performance were collected, and CT was performed, at regular intervals every 6 to 12 months. Psychomotor skills showed the most significant and consistent decline among the cognitive functions assessed. Memory disturbances were already present at the time of enrollment, but memory did not deteriorate until patients reached advanced stages. Other cognitive operations, such as visual construction and semantic knowledge, manifested small and variable changes over time. CT indices of striatal atrophy correlated only with changes in psychomotor function, while the CT index of frontal atrophy weakly predicted memory and semantic knowledge scores at 42 months. These results confirmed earlier cross-sectional findings and extended our knowledge of the evolution of cognitive dysfunction in HD.

Physiologic effects of contrast media in the rabbit.

The intravenous administration of contrast media (CM) is often associated with alterations in blood pressure (BP) and heart rate (HR). Osmolality is thought to play a role, but the magnitude and even the direction of change may vary under similar osmotic conditions indicating the involvement of other mechanisms. Conscious rabbits received sodium-meglumine diatrizoate (76%, 1 mL/kg, ear vein) every 10 minutes for 1 hour. A similar injection protocol was performed with normal saline and mannitol (36%), equiosmotic to the contrast agent. BP and HR were monitored continuously. Blood samples were collected at the midpoint between each injection for determination of hematocrit, serum osmolality, and iodine concentration. Group parameters at each time point were compared with the Student's t-test. The administration of mannitol caused changes in serum osmolality, hematocrit, and HR as great or greater than the changes caused by equiosmotic diatrizoate. However, BP increased significantly in the diatrizoate group but not in the mannitol group, relative to normal saline. These results suggest that osmolality is important for certain physiologic changes induced by CM, but that BP changes involve mechanisms in addition to osmolality.

The role of nonionic myelography in the diagnosis of lumbar disc herniation.

RATIONALE AND OBJECTIVES: The accuracy and safety of nonionic myelography, unenhanced computed tomography (CT), and magnetic resonance (MR) in the diagnosis of lumbar disc herniation are reviewed. The comparative costs of these tests are also considered. METHODS: The accuracy of imaging tests that diagnose disc herniations was established by conducting a Medline search between 1985 and 1992. The morbidity associated with these tests are less formally established from selected articles. Finally, the mediocre reimbursement rates of these tests are reviewed. RESULTS AND CONCLUSIONS: The evolution of nonionic contrast media from the first to the second generation has been accompanied by a notable decrease in adverse reactions. Although nonionic myelograms are now better tolerated by patients, noninvasive imaging with CT and MR imaging has become as accurate as or more accurate than lumbar myelography, and should replace it as a screening test. Computed tomography may have advantages over MR imaging when issues of availability and cost are considered. In contrast to lumbar myelography, CT myelography may continue to be a useful method for clarifying ambiguous results of noninvasive tests. The morbidity associated with CT myelography can be minimized by using low doses of a nonionic agent, keeping the patient well hydrated, and using a small lumbar puncture needle. The incidence of adverse reactions can be expected to decrease further as new nonionic dimers become clinically available.

Opiate involvement in contrast media-induced blood pressure changes.

The intravenous administration of contrast media (CM) often alters blood pressure (BP). Osmolality plays a role, but the magnitude and even direction of change varies under similar (osmotic) conditions, indicating the involvement of other mechanisms. Male Wistar rats, anesthetized with pentobarbital, received sodium/meglumine diatrizoate, iohexol, or normal saline, 4 ml/kg, via a tail vein, while blood pressure was recorded continuously. Additional groups were pretreated with the opiate antagonist, naloxone (1 mg/kg, IV), or with an equal volume of normal saline 5 minutes prior to the diatrizoate injection. Comparisons of BP change were made with the Student's t-test. Diatrizoate caused a significant (P less than .0002) increase in BP relative to the saline control group, iohexol did not. Thus, the increase with diatrizoate was significantly greater than with iohexol (P less than .00006). Neither the saline nor naloxone pretreatment altered BP significantly. Saline pretreatment did not alter the significant increase in BP produced by the diatrizoate. However, the diatrizoate-induced increase in BP was prevented by the naloxone pretreatment and was significantly less than after the saline pretreatment (P less than .0001). Based on these and previous results, the authors hypothesize that release of endogenous opioids may play a role in BP changes caused by intravenous CM and that significant CM-induced changes may be prevented pharmacologically with the selective opiate blocker, naloxone.

The role of catheters and guidewires in the production of angiographic thromboembolic complications.

Thromboembolic complications occurring during angiography may result from a number of different causes. Catheters and guidewires can interact with blood to form thrombi; this tendency is related to wall defects and the chemical composition and structural characteristics of the catheters and guidewires. Nonthrombic sources of emboli may consist of foreign bodies derived from surgical equipment or may exist in the flushing solution and contrast media. Plastic emboli may be shed from catheters and guidewires when the guidewires are passed through the catheters. Air emboli may result from poor technique or loose fitting connections between the catheter and injector or syringe; they can mimic emboli from catheters and guidewires. A number of strategies for decreasing the risk of thromboembolic complications during angiography are reviewed.

Effect of multiple intravenous injections of diatrizoate on iodine concentrations and osmolality. An experimental study in rabbits.

Multiple intravenous injections of contrast media are used in radiology, but information regarding corresponding changes in the serum iodine concentrations and osmolality is lacking. We measured the changes in serum iodine concentration and serum osmolality in rabbits after a series of intravenous injections of contrast media. Hypaque-76 (1 cc/kg) was injected intravenously in awake rabbits at 10-minute intervals for 1 hour and arterial blood sampled at midpoint times between injections. During the 1-hour period of seven serial injections, mean serum iodine concentration at 5 minutes was 2.3 mg I/cc (+/- 0.1 SEM, n = 14); at 35 minutes, 5.1 mg I/cc (+/- 0.2); and at 65 minutes, 6.7 mg I/cc (+/- 0.4). The mean peak concentration was 6.8 mg I/cc (+/- 0.4). Serum osmolality underwent a mean increase of 16 mosm/kg during the injection period. Hypertonic mannitol injections produced a smaller increase in osmolality (10 mosm/kg). Isotonic saline injections in control animals produced no change in osmolality.

Pharmacokinetics and excretion of iohexol after lumbar myelography in man.

Pharmacokinetics and excretion of iohexol, a new nonionic water-soluble contrast medium, were determined after lumbar myelography. Peak plasma concentrations were obtained 2 to 6 hours after injection and ranged from 29 to 177 microgram/ml. Terminal elimination half-life was 4.0 hours, and over 90% of the dose was recovered in the urine within 24 hours. In one patient with a large lumbar cauda equina tumor, absorption and excretion were delayed; but eventually 99% was recovered indicating a large capacity for reabsorption via the lumbar subarachnoid space. One mild headache of 5 minutes' duration was reported in a 73-year-old woman. No significant changes in vital signs, neurologic examinations, or serum chemistries were observed.

The effect of iohexol on glucose metabolism compared with metrizamide.

In a previous in vitro study we demonstrated reduced CO2 production in rat hippocampal tissue when metrizamide was added. This metabolic depression is believed to be a result of the 2-deoxy-D-glucose (2-DG) portion of the metrizamide molecule since 2-DG is a known competitive inhibitor of glucose metabolism. This competitive inhibition probably occurs at the cell membrane since it has never been shown that metrizamide penetrates neural cells. Further the inhibition is most likely related to competition for the membrane glucose carrier. A new nonionic contrast medium, iohexol, does not contain a 2-DG component and if the hypothesis for the metabolic inhibition is valid we should not expect metabolic inhibition with iohexol. This hypothesis was tested using the rat hippocampus model previously used for metrizamide. We compared iohexol with metrizamide in isotonic concentrations and also examined the effect of hypertonicity. These experiments did not demonstrate inhibition of CO2 production with iohexol at near physiologic osmolalities, however, there was a marked depressive effect with increasing osmolality. This effect from hypertonicity is, however, probably of less importance in vivo where water will rapidly diffuse toward the hypertonic areas. The apparent lack of interference of the iohexol molecule on glucose metabolism should therefore make iohexol a more suitable contrast medium, for subarachnoid investigations than metrizamide.

Lumbar myelography with iohexol and metrizamide. A comparative multicenter prospective study.

Diagnostic quality and adverse reactions associated with metrizamide and iohexol as contrast agents for lumbar myelography were compared in a prospective randomized double-blind study in 350 patients at seven centers. Both contrast media were administered in comparable volumes at a concentration of 180 mg I/ml. Overall quality of radiographic visualization was graded as "good" or "excellent" in 95% of 175 metrizamide studies and in 98% of 175 iohexol myelograms. Ninety-three patients examined with metrizamide (53%) and 130 patients studied with iohexol (74%) experienced no discomfort during or after myelography. The incidence of postmyelographic headache was 38% with metrizamide and 21% with iohexol. Nausea and vomiting were also more common with metrizamide. Five patients examined with metrizamide (3%) experienced transient confusion and disorientation after lumbar myelography. No such reactions were observed after iohexol myelography.

Iohexol cerebral angiography. Multicenter clinical trial.

Ionic contrast media currently used in cerebral angiography frequently cause discomfort due to hyperosmolality. This double-blind, multicenter trial compared two ionic media, meglumine iothalamate and meglumine-Na diatrizoate, with the new nonionic agent, iohexol, in 277 patients undergoing cerebral angiography. Vital signs, cardiovascular changes, and neurologic status were evaluated before, during, and after injection. Patients were observed for adverse reactions for up to 24 hours following studies. Patient discomfort and image quality were evaluated. Visualization was good or excellent with all media studied. No significant physiological differences were observed between the ionic and iohexol groups, but fewer iohexol patients experienced large increases (greater than 20 mmHg) in systolic blood pressure. Iohexol patients experienced significantly less discomfort; ionic patients reported severe discomfort 21/2 times more often. This finding was attributed to iohexol's low osmolality. Iohexol may be indicated particularly for use in selective angiograms where discomfort is a factor and for patients suspected of having blood-brain barrier disruption.

Temporal lobe atrophy in patients with Alzheimer disease: a CT study.

CT was used to document temporal lobe atrophy in 39 patients who were diagnosed clinically as having Alzheimer disease; the results were compared with those from 29 healthy elderly control subjects who were matched for age and education. The diagnosis of Alzheimer disease was made according to clinical criteria consistent with those specified by an NINCDS workshop. These included detailed medical and neuropsychological assessments. Temporal lobe atrophy was assessed by evaluating the temporal horns and sylvian cisterns. Temporal horn measurements greater than 3 mm occurred only in patients with Alzheimer disease while measurements less than or equal to this occurred in both Alzheimer patients and control subjects. Subjective evaluation of the sylvian cistern indicated that 24/29 controls had normal-appearing cisterns while only 5/39 Alzheimer patients had similar findings. In contrast to temporal horns, sylvian cisterns were more sensitive but less specific as discriminators between Alzheimer patients and normal controls.

Iohexol lumbar myelography: clinical study.

Forty-three patients underwent lumbar myelography with the new, nonionic contrast medium iohexol. Multiple laboratory examinations, neurologic examinations, and electrocardiograms showed no significant alterations after intrathecal injection of the contrast agent. Mild electroencephalographic changes were seen in one patient. Nineteen adverse reactions occurred in 13 patients; only one of them was considered severe. No patient experienced a seizure, auditory or visual hallucination, or similar neuropsychologic reaction. This is a distinct improvement over the side effects described for previous water-soluble contrast agents. The adverse reactions occurring with iohexol myelography are fewer in number and less severe than with metrizamide myelography, and radiographic visualization obtained with iohexol is equal to that obtained with metrizamide. With iohexol, it appears that the most disturbing and disabling neuropsychologic reactions have been reduced to an acceptable minimum.

MR high-resolution blood oxygenation level-dependent venography of occult (low-flow) vascular lesions.

A new technique for detecting vascular malformations, high-resolution BOLD venography (HRBV), is described. This technique relies on the BOLD principle for detecting deoxygenated blood in low-flow malformations. HRBV images are acquired using a modified 3D gradient-echo with voxel volumes of 0.5 x 0.5 x 2 mm3. The magnitude data are masked with the phase images to enhance visibility of the venous structures and are displayed using the minimum intensity projection. Preliminary results for 10 patients show that HRBV is more sensitive in detecting cavernomas than is T2-weighted imaging, and lesions that are presumed to be telangiectasias are detected only with this technique.

A comparison of default and reduced bandwidth MR imaging of the spine at 1.5 T.

The value of a reduced bandwidth MR imaging technique was tested prospectively in 51 spinal MR examinations by using default (16 kHz) bandwidth, 2000/30, 90 (TR/TEs) and 600/30, and reduced (8 kHz) bandwidth, 2000/48, 92 and 600/30, techniques at 1.5 T. Bandwidth reduction was used to maintain the signal-to-noise ratio for a reduced scan time. Concerns have been raised as to the effect of bandwidth reduction at high field, since a savings in time or an increased signal-to-noise ratio occur at the expense of increased chemical shift misregistration artifact. However, when appreciable, the chemical shift-related artifact in the spine was typically located in the frequency-encoding direction at the vertebral body/disk space interface or the dural sac/epidural fat interface in the lower lumbosacral region and was easily distinguished from pathologic lesions. There were no missed diagnoses with the reduced bandwidth technique. This study suggests that chemical shift-related artifact will rarely be confused with pathology by an experienced reader and suggests a clinical role for the bandwidth technique to decrease scanning time in uncooperative patients or to allow acquisition of additional imaging planes in a reasonable time.

New imaging techniques in diagnosis of cerebrospinal fluid fistula.

The localization of a cerebrospinal fluid fistula producing cerebrospinal fluid otorrhea can be very difficult. However, the exact anatomic localization of the bony defect is important when selecting the surgical approach to repair. Case reports of two patients in whom spontaneous cerebrospinal fluid otorrhea occurred following pressure equalization tube placement for middle-ear effusion are presented. Nuclear magnetic imaging supplemented CT scan findings, providing noninvasive localization of the defect. Preoperative impressions were confirmed at surgery. In addition to discussing the use of magnetic resonance imaging in evaluating cerebrospinal fluid otorrhea, the literature will also be reviewed.

Gadolinium-DTPA-enhanced magnetic resonance scanning in cerebellopontine angle tumors.

Magnetic resonance (MR) imaging has quickly emerged and already replaced computerized tomography (CT) in the evaluation of cerebellopontine angle (CPA) lesions, although even MR scanning may occasionally yield equivocal results. We recently studied six patients with a new MR image-enhancing contrast, gadolinium-DTPA (Gd-DTPA). All patients were suspected of having CPA pathology, and the standard MR scan was either negative, equivocal, or left unanswered questions regarding confirmed lesions. The Gd-DTPA-enhanced MR scan confirmed tumors or added useful information in five of six patients.

Moyamoya disease in an infant with autonomic dysfunction: angiographic and MRI findings.

An infant with persistent Harlequinism went on to develop a hemiparesis secondary to Moyamoya disease at 2 1/2 months of age. The sympathetic nervous system is proposed to be an etiologic factor in the pathophysiology of Moyamoya disease as well as Harlequinism. This is one of the youngest patients reported in the English literature with Moyamoya disease and the only report of the coexistence of Moyamoya disease and atypical Harlequinism. Magnetic resonance imaging led to the diagnosis, which was confirmed by cerebral angiography.