Pamidronate reduces PTH-mediated bone loss in a gene transfer model of hyperparathyroidism in rats.

We evaluated spinal and femoral bone mass and density utilizing dual-energy x-ray absorptiometry (DEXA) in rats in which severe hyperparathyroidism was produced by the expression of the gene for human PTH-(1-84) (hPTH). This gene was incorporated into a retroviral vector that was transfected into fibroblasts which were subsequently injected into their peritoneal cavities. Further, we examined the effect of the administration of pamidronate on bone mass and density in the presence of extremely high concentrations of hPTH. Three groups of rats were studied. Groups 1 and 2 receive the hPTH-secreting fibroblasts; group 2 subsequently received pamidronate (2.5 mg/kg IV) 18 and 27 days after receiving the fibroblasts. These animals developed levels of hPTH greater than 1.0 microgram/liter and became hypercalcemia within 20 days. These animals became lethargic and were significantly lower in weight than age-matched controls (group 3, p less than 0.05). After accounting for the animal weight there was a further significant decrease in bone mineral content and density (BMC and BMD) on day 29 attributable to hPTH-mediated bone loss. Treatment with pamidronate resulted in a higher BMC of the lumbar spine than in the untreated animals, with elevated concentrations of hPTH. The BMD was significantly higher at both the lumbar spine and femur in the pamidronate-treated animals (p less than 0.05). The CV of paired measurements of BMD was 2.7% at the spine and 1.5% of a femur, respectively. The BMC of the lumbar spine and femur was closely correlated with the ashed weight of the same bones (r = 0.92 and 0.85, respectively).

Lateral and third-ventricular CSF formation after metrizamide CT ventriculography.

We calculated the rates of lateral and third-ventricular (LTV) cerebrospinal fluid (CSF) formation in three patients undergoing metrizamide computed tomography (CT) ventriculography with reference to Ct estimates of ventricular volume and the time course of LTV metrizamide washout (elimination). Elimination rate constants for metrizamide were derived from measurements of LTV metrizamide concentration on serial postventriculography CT scans, and LTV volumes were estimated by partial volume analysis. CSF formation in the combined lateral ventricles averaged 0.14 ml per minute, and third-ventricular CSF formation averaged 0.014 ml per minute. Thus, the third ventricle accounted for approximately 10% of total LTV CSF production, which accords with relative weights of choroid plexus tissue in the lateral and third ventricles.

Nonmetastatic superior sagittal sinus thrombosis complicating systemic cancer.

Seven patients with cancer complicated by nonmetastatic sagittal sinus thrombosis were encountered in a 7-year period. Five had hematologic malignancies and two had solid tumors. There were two different presentations. In the first, neurologic signs and symptoms (e.g., headaches, seizures, hemiparesis, lethargy) occurred suddenly in five patients shortly after initiation of cancer therapy. Four of these five patients recovered with minimal residua; the fifth died as a direct result of the sinus thrombosis. The second presentation occurred in the two patients with terminal cancer who declined gradually without focal signs; both patients died. Only arteriography can reliably establish the diagnosis of sagittal sinus occlusion. In patients with cancer, sagittal sinus occlusion probably results from a "hypercoagulable state" associated with the systemic neoplasm.

Pituitary metastasis: incidence in cancer patients and clinical differentiation from pituitary adenoma.

Symptomatic pituitary metastases are uncommon and may be difficult to differentiate from pituitary adenomas. In order to ascertain the incidence of pituitary tumors in cancer patients and to characterize the clinical presentation of pituitary metastases, we reviewed the clinical experience with these tumors at Memorial Sloan-Kettering Cancer Center (MSKCC) during the period 1976-1979 and a recent series of 500 consecutive autopsies in which the pituitary fossa and gland were examined. In the clinical series, a histologic diagnosis was made in three of five patients. Radiologic evaluation, including polytomography and computed tomography, did not reliably distinguish metastasis from adenoma, but the clinical syndromes were distinctive. In the autopsy series, pituitary metastases were found in 3.6% of cases, pituitary adenomas in 1.8%.

MRI changes in intracranial hypotension.

We report seven patients with the syndrome of intracranial hypotension who were referred to Memorial Sloan-Kettering, primarily because of suspicion of meningeal tumor or infection raised by the finding of meningeal enhancement on MRI. In three patients, symptoms occurred after lumbar puncture; in four, there was no clear precipitating event. Lumbar puncture after MRI in six patients revealed low CSF pressure (six patients) and pleocytosis or high protein, or both (four patients). Three patients had subdural effusions. Six patients had measurable descent of the brain on midsagittal images. Postural headache resolved in all seven patients, six of whom had follow-up MRIs. Meningeal enhancement resolved or diminished in all six. Subdural effusions resolved spontaneously in two and were evacuated (but were not under pressure) in one. Downward brain displacement improved or resolved in all patients. The clinical syndrome and MRI abnormalities generally resolve on their own. An extensive workup is not helpful and may be misleading. Patients should be treated symptomatically.

Metastasis to the base of the skull: clinical findings in 43 patients.

We studied 43 patients with metastases to the base of the skull to determine whether clinical symptoms localized the lesions accurately. We identified five clinical syndromes: orbital, parasellar, middle fossa, jugular foramen, and occipital condyle. The orbital and parasellar syndromes were characterized by frontal headache, diplopia, and first-division trigeminal sensory loss. Proptosis occurred with the orbital but not the parasellar syndrome. The middle-fossa syndrome was characterized by facial pain or numbness. The jugular foramen syndrome was characterized by hoarseness and dysphagia, with paralysis of the ninth through eleventh cranial nerves. The occipital condyle syndrome was characterized by unilateral occipital pain and unilateral tongue paralysis.

MRI assessment of human callosal surgery with neuropsychological correlates.

MRI imaging using recovery and spin-echo techniques was carried out on three patients after surgical section of the corpus callosum to control intractable epilepsy. The scans revealed that the total callosotomy had been obtained in two patients, while partial sparing of splenial and rostral fibers was seen in the third.

Direct in vivo observation of transventricular absorption in the hydrocephalic dog using magnetic resonance imaging.

RATIONALE AND OBJECTIVES: A model of chronic noncommunicating hydrocephalus in canines was developed, and gadolinium-DTPA (Gd-DTPA)-enhanced magnetic resonance imaging, physiologic and morphologic studies were performed to investigate transventricular absorption of cerebrospinal fluid. METHODS: Chronic hydrocephalus was induced in 12 mongrel dogs by injection of a silastic mixture into the prepontine cisterns. Ventricular pressure was measured during the development of hydrocephalus, and lateral ventriculo-ventricular perfusions with Gd-DTPA were performed under controlled conditions during serial magnetic resonance imaging studies. RESULTS: Hydrocephalus developed over an average of 129 +/- 24 days after induction, and the intraventricular pressure increased from an initial level of 14 +/- 4 cm H2O to a stabilized plateau of 25 +/- 5 cm H2O. Increased signal intensity in the brain matter, as seen on magnetic resonance images of chronic hydrocephalic dogs perfused with Gd-DTPA in the lateral ventricles, was consistent with the presence of the contrast agent in the periventricular extracellular space. This increased signal intensity was not observed in control animals. CONCLUSIONS: These results provide direct evidence of transventricular absorption in chronic hydrocephalus.

MR imaging of cerebral vascular malformations.

Fifteen vascular malformations, including six supratentorial arteriovenous malformations (AVMs), three venous malformations, and six brainstem vascular malformations, were examined on 0.5 T magnetic resonance (MR) and GE 9800 and 8800 computed tomographic (CT) scanners. All the malformations were shown by MR, and the arterial and venous drainage of AVMs was precisely delineated. Hematoma was always differentiated from calcification by MR signal characteristics. Increased signal in the brain parenchyma was often seen adjacent to AVMs. The signal of blood within venous malformations altered with spin-echo techniques using various repetition times and was distinguished from rapidly flowing blood in AVMs that lacked signal in all imaging sequences. Brainstem malformations were seldom demonstrated by angiography. Hemorrhage was common and was invariably associated with multiple areas of absent signal that may have represented abnormal vessels. These appearances are distinct from those of intrinsic tumors and are probably pathognomonic of brainstem vascular malformations.

MRI of optic chiasm and optic pathways.

Eight verified lesions of the optic chiasm were examined on 0.5 T magnetic resonance (MR) and GE 9800, 8800 computed tomographic (CT) scanners. Enlargement of the optic chiasm was demonstrated in all cases. There was some change of MR signal compared with brain in all but one case, which had no resemblance to contrast enhancement on CT scans. The signal was specific for hematoma in one case. Abnormal signal, probably signifying tumor spread into the optic radiation, was detected on T2-weighted images in one case. The resolution of MR scans is similar or superior to CT, and sagittal views are most useful in evaluating lesions in this location.

Optimization of xenon-enhanced CT studies: beam energy, enhancement, root mean square deviation, and repeatability.

The effects of varying beam energy on the computed tomographic (CT) enhancement-to-noise (S:N) ratio were studied experimentally with the DeltaScan 2020 and GE 8800 CT scanners and a 20-cm-diameter cyclindrical Plexiglas phantom containing 11 50 ml syringes filled with varying amounts of xenon and iodine. Enhancements of 54.2, 36.7, and 31.7 Hounsfield units (H)/mg l/ml were measured with the DeltaScan 2020 at 70, 100, and 120 kVp, respectively, with corresponding root mean square deviations (RMSDs) of 12, 7, and 5 H for 400 mAs scans. For the GE 8800, enhancements of 48.3, 37.6, and 32.7 H/mg l/ml were measured at 80, 100, and 120 kVp with RMSDs of 13, 8, and 7 H for 9.6 sec 320 mA scans (3.3 msec pulse). RMSD was independent of enhancement over the range of iodine concentrations studied (0-1.5 mg l/ml) and was only a weak function of region-of-interest (ROI) size. For repeated scans with the DeltaScan 2020, measurements in 17 X 17 pixel regions were reproducible to within 0.8 H for all techniques and a drift in calibration of less than 6% was observed after 8 months of clinical use. For both the DeltaScan 2020 and the GE 8800, at the milliamperage studied, lower-energy techniques offered no advantage over 120 kVp technique for xenon CT measurements of regional cerebral blood flow, which are feasible using either of these scanners.

Detection of acute intracerebral hemorrhage on MR imaging: ineffectiveness of prolonged interecho interval pulse sequences.

MR imaging at 0.6 T was performed in 22 patients with acute (less than 7 days) intracranial hemorrhage to determine the efficacy of prolongation of the interecho interval, which has been demonstrated to enhance T2 shortening in vitro, as a method to improve the detection of hemorrhage in clinical imaging. The protocol included 750/33 (TR/TE), 2150/60,120 (short interecho interval of 60 msec), and 2150/120 (long interecho interval of 120 msec) sequences. Visual comparisons of the 2150/120 images obtained with the short and long interecho intervals demonstrated no difference in the degree of hypointensity in 21 of 22 cases. Quantitative comparisons demonstrated no statistically significant difference in the degree of maximal hypointensity, in the ease of detectability of hypointensity, or in the overall image contrast in 16 of 22 cases. We conclude that prolongation of the interecho interval is not a clinically useful technique to improve the detection of acute hemorrhage.

Dural sinus thrombosis: verification with spin-echo techniques.

Although MR imaging is being used increasingly to detect dural sinus thrombosis, accurate evaluation of images has often been hindered by the presence of artifacts, especially flow-related enhancement, that may simulate intraluminal clot. We tried an approach with spin-echo techniques to eliminate flow-induced artifacts and, thus, facilitate the diagnosis of dural sinus thrombosis. In this investigation, a nonselective single-section spin-echo verification method was used as a prototype of this approach. Both patients and an experimental flow phantom were used to test the validity of this concept. Clinically, thrombosis was seen to persist as isointense or highly intense signal in the vascular lumina with the specialized sequence, while flow-related artifacts were replaced by hypointense signal, but not by signal void. These same changes were examined both quantitatively and qualitatively in the flow phantom by using varying velocities of flow. Although our clinical investigation concerns suspected dural sinus thrombosis, the principles of these specialized spin-echo techniques can be applied successfully throughout the head to eliminate certain flow-related artifacts.

Differentiation between meningeal fibrosis and chronic subdural hematoma after ventricular shunting: value of enhanced CT and MR scans.

Unenhanced CT in four patients with long-standing ventricular shunts demonstrated bilateral low-density extraaxial collections that were indistinguishable from chronic subdural hematomas. After administration of contrast material, however, there was marked enhancement of the collections as well as prominent paratentorial and parafalcial enhancement. MR imaging, performed in three patients, demonstrated the extent and paradural location of the collections better than CT did, but, as with unenhanced CT, the collections could not be distinguished from chronic subdural hematomas. On follow-up CT and MR, there was no change in the size, enhancement, or intensity of the collections. Histologic examination of biopsies from two patients demonstrated fibrosis of the meninges characterized by granulation tissue and collagen deposition. Meningeal fibrosis is a rare postshunt phenomenon that may mimic chronic subdural hematoma on unenhanced CT and MR. Recognition of this entity is important, particularly if therapeutic intervention is being considered. Therefore, an enhanced CT or enhanced MR scan should be obtained in chronically shunted patients to differentiate between a drainable chronic subdural hematoma and meningeal fibrosis.

Large Virchow-Robin spaces: MR-clinical correlation.

High-field MR scans frequently show Virchow-Robin spaces, which conform to the path of the penetrating arteries as they enter either the basal ganglia or the cortical gray matter over the high convexities. A retrospective review of 816 MR scans was undertaken to determine the clinical significance and associations (if any) of this finding. The Virchow-Robin spaces were graded, as were the nonspecific white-matter lesions. The presence of atrophy, infarction, hydrocephalus, and miscellaneous disease was noted. Large Virchow-Robin spaces were identified in 314 cases. A study sample was created consisting of a positive group containing all the larger grade 2 and 3 Virchow-Robin spaces (67 patients) and a negative or control group of 109 randomly selected patients from the original 502 who did not have large Virchow-Robin spaces. The charts of this study sample were reviewed and the following patient variables were noted: age, gender, incidental white-matter lesions, infarction, dementia, hypertension, and atrophy. For each variable, the proportion of patients who were positive for that variable was calculated for each of the two groups and compared across groups by using a Fisher exact test. Multiple logistic regression analysis was used to determine whether any of these variables were jointly associated with being "positive" or "negative" for large Virchow-Robin spaces. Some variables were strongly associated with being positive for large Virchow-Robin spaces: age, hypertension, dementia, and incidental white-matter lesions. Logistic regression analysis revealed that when all of these variables are considered jointly, only age remains significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal cocaine abuse: the spectrum of radiologic abnormalities in the neonatal CNS.

The purpose of this study was to determine the pattern and frequency of CNS abnormalities in the offspring of cocaine-abusing mothers. The study group consisted of a retrospective review of all neonates born or admitted to our neonatal intensive care unit over a 1-year period who met criteria for maternal cocaine abuse (43 patients). A control group (62 patients) was obtained from patients seen during the same interval and the cases were matched for gestational age and race. The radiologic studies were analyzed by two independent reviewers, and CNS abnormalities were assessed by means of sonography, CT, or MR. By matching the study and control groups for gestational age, we eliminated the higher frequency of prematurity. This allowed us to determine if maternal cocaine use was associated with any intracranial abnormalities other than those seen with prematurity. The frequency of intracranial hemorrhage, ventricular enlargement, and periventricular leukomalacia was not significantly different between the study and control groups. The frequency of cortical infarction was 17% in the study group and 2% in the control group. The frequency of major congenital malformation was 12% in the study group and 0% in the control group. All five of the congenital malformations seen were midline CNS abnormalities, particularly neural tube defects. It is postulated that the higher statistically significant frequency of stroke and congenital malformations in the babies of maternal cocaine abusers is related to vasospasm caused by cocaine when used in the third and first trimesters, respectively.

MR imaging of the craniocervical junction.

Craniocervical junctions in 35 abnormal and 10 normal subjects were studied with a 0.5 T superconducting magnetic resonance imaging system. Sagittal spin echo with 30 msec echo times and 500 msec repetition times constituted the most informative imaging plane and sequence. The anterior aspect of the foramen magnum was well delineated; the posterior margin was less constant in appearance. Compression and distortion of the medulla and upper cervical cord by bony and extramedullary lesions were seen easily. Intramedullary cysts were differentiated from solid tumors, but ventricular communication was evaluated less successfully because of partial-volume effect of the sections. Cerebellar ectopias were detected in some asymptomatic patients.

MR recognition of supratentorial tumors.

Eighty patients with intrinsic tumors of the cerebral hemispheres and thalami were studied with a 0.5 T superconducting system and third- or fourth-generation computed tomographic (CT) scanners. Twenty-eight patients had histologically verified gliomas, 34 were presumed to have primary brain tumors on clinical grounds, 13 had metastases, and five were postoperative. Lesions shown on CT were equally well demonstrated on magnetic resonance (MR) imaging; more metastases were seen on MR than on CT images. MR revealed abnormal signals in 10 cases in which CT findings were equivocal. It was not possible to differentiate edema from tumor in many cases using the MR imaging sequences currently available. The histologic types of the tumors could not be determined from the MR appearances.

MR imaging of acute intracranial hemorrhage: findings on sequential spin-echo and gradient-echo images in a dog model.

Seven intraparenchymal hematomas (four venous and three arterial) were placed in the brains of six dogs in order to study the MR appearance of acute hemorrhage and to evaluate the effects of several variables on the signal intensity of the hematoma. MR imaging at 0.6 and 1.5 T was performed by using standard short and long TR spin-echo and low-flip-angle gradient-echo sequences. Sequential examinations were performed during the first week following hematoma creation. MR findings were compared with CT and postmortem examinations. Three patterns of signal intensity were observed, which varied according to the size (small vs large) and location (parenchymal vs intraventricular) of the hematomas. The small parenchymal hematomas did not undergo evolutionary changes. On short TR scans they were isointense at both field strengths, and therefore not detectable; on long TR scans these hematomas were of variable intensity at 1.5 T and were hyperintense at 0.6 T. On gradient-echo scans, they were hypointense at all times at both field strengths. The large parenchymal hematomas underwent evolutionary changes typical of those seen in clinical imaging. On short TR scans they were initially isointense and became hyperintense 1-3 days later. Long TR scans demonstrated initial hyperintensity, followed by the development of hypointensity within 12 hr in the venous hematomas and within 60 hr in the arterial hematoma. The intensity changes on long TR scans were seen at both 0.6 and 1.5 T, but occurred sooner and to a greater degree at 1.5 T. Gradient-echo imaging of these large lesions demonstrated hypointensity at all times at both field strengths. The intraventricular hemorrhages demonstrated more rapid development of hyperintensity on short TR scans and slower and less pronounced development of hypointensity on long TR scans compared with the parenchymal clots in the same animal. Gradient-echo imaging of the intraventricular hemorrhages demonstrated hypointensity at all times at both field strengths. A multifactorial hypothesis is proposed to explain the differences in intensity between venous, arterial, and intraventricular blood. Gradient-echo sequences should prove to be highly useful in detecting and delineating hemorrhages and are recommended for the MR protocol of patients with acute neurologic ictus and suspected hemorrhage.

A canine model of acute hydrocephalus with MR correlation.

Within 3 hours of induction of acute hydrocephalus in a canine model, lateral ventricular CSF pressure increased from an initial average of 14.6 +/- 2.8 cm H2O to 40.2 +/- 5.7 cm H2O. Ventricular volumes, as measured from MR images, increased 1.45 +/- 0.94 cm3, 1.92 +/- 0.82 cm3, and 2.24 +/- 0.60 cm3 after 6, 24, and 48 hours, of hydrocephalus, respectively. This canine model was reliable and consistent with clinical conditions.