Secretory and nonsecretory pituitary adenomas are distinguishable by 1/T1 magnetic relaxation rates at very low magnetic fields in vitro.

RATIONALE AND OBJECTIVES: The authors investigated whether hormonally active and inactive pituitary adenomas can be discriminated in vitro by magnetic resonance (MR) imaging-related data. METHODS: 1/T1 nuclear magnetic relaxation dispersion profiles were measured for 39 fresh surgical specimens of secreting and nonsecreting adenomas, classified using clinical criteria or preoperative serum hormone levels. Nonsecreting adenomas were subdivided into hormone-producing and nonhormone-producing by immunostains. At five fields (0.00024 to 1.2 tesla [T]), mean 1/T1 was analyzed for statistically significant differences among these three tumor categories. RESULTS: Mean 1/T1 was significantly higher (P < 0.02) for hormone-secreting than for nonsecreting adenomas at fields below 0.24 T; no significant difference existed at typical MR imaging fields (0.5 to 1.5 T). Mean 1/T1 for hormone-producing and nonhormone-producing, nonsecreting adenomas were not significantly different at any field. CONCLUSIONS: Because 1/T1 at low fields is related to 1/T2 at imaging fields, it may be possible to detect hormone secretion of pituitary adenomas noninvasively by MR imaging.

Calcification can shorten T2, but not T1, at magnetic resonance imaging fields. Results of a relaxometry study of calcified human meningiomas.

RATIONALE AND OBJECTIVES: Water content and water-proton relaxation rates are reported for fresh, histologically characterized, surgical specimens of calcified human intracranial meningiomas and compared with results for noncalcified meningiomas from an earlier study and with calcium hydroxyapatite (CaHA) suspensions to elucidate the influence of calcification on magnetic resonance imaging (MRI) signal intensity of calcified meningiomas. METHODS: The magnetic field dependence of 1/T1 of water protons (nuclear magnetic relaxation dispersion profile) and dry weights are reported for 38 calcified nonhemorrhagic and 3 hemorrhagic specimens of known histologic subtype, a subset of the 67 specimens measured earlier. Calcification was considered mild or heavy when the dry weight was within or above the range for noncalcified meningiomas. Preliminary 1/T1 profiles for pure CaHA and a single high-field 1/T2 value also are reported. RESULTS: The ranges of dry weights and of low-field 1/T1 values were twice as large for calcified as for noncalcified meningiomas. No correlation was found between low-field 1/T1 and either histologic subtype or dry weight. Mild calcification produced the highest low-field 1/T1 values; the most heavily calcified tumor had slightly increased low-field 1/T1. Calcium hydroxyapatite increases low-field 1/T1 significantly but not high-field 1/T1; high-field 1/T2 is large. For calcified hemorrhagic meningiomas, increases in both low-field and high-field 1/T1 were seen. CONCLUSION: For mild calcification, MRI signal voids result from an increased high-field 1/T2; for heavier calcification, reduced proton density (from excluded water) becomes of increasing importance. Cellular CaHA appears to brighten the signal in T1-weighted MRI in the presence of hemorrhage.

A cytomorphological scheme of differentiating neuronal phenotypes in cerebellar medulloblastomas based on immunolocalization of class III beta-tubulin isotype (beta III) and proliferating cell nuclear antigen (PCNA)/cyclin.

This immunohistochemical study compares the localization of the neuronal class III beta-tubulin isotype (beta III) to that of the proliferating cell nuclear antigen (PCNA)/cyclin in 46 cerebellar neuroblastic tumors (medulloblastomas). Both class III beta-tubulin (beta III) and PCNA/cyclin reactivities were present in all tumors, but the topographic distribution and cytomorphologic features of stained cells varied considerably between classic and desmoplastic medulloblastomas. Four neoplastic phenotypes, representing gradations of neuronal differentiation, were identified: [Allegranza 1991] apolar, blast-like PCNA/cyclin(+) cells devoid of beta III reactivity (Nb1); [Bravo et al. 1987] apolar, often binucleated and/or fusiform, PCNA/cyclin (+) cells with pronounced beta III staining in their protoperikarya and their growth cones (Nb2); [Burger et al. 1987] beta III-immunoreactive immature polar neurons with varying degrees of neuritic development, reading to significant neuritogenesis in the "pale islands" of desmoplastic medulloblastomas (Nb3). The majority of Nb3 phenotypes were PCNA/cyclin (-), although subpopulations of such polar tumor cells exhibiting PCNA staining were also identified; and [Burger et al. 1991] beta III-immunoreactive, PCNA/cyclin (-) mature ganglion-like cells (Nb4). A high PCNA/cyclin labeling index (> 80%) was obtained in 20 poorly differentiated classic medulloblastomas while, significant intratumoral staining heterogeneity was observed in 23 cases of desmoplastic medulloblastomas and 3 cases of "medulloblastomas with ganglion cells": A high labeling index (LI)(> 80%) in the reticulin-impregnated poorly differentiated areas of tumor contrasted with sharp decline of PCNA staining and a very low LI (< 10%) in areas of overt neoplastic neuritogenesis ("pale islands") displaying strong beta III reactivity. Neoplastic ganglion cells were beta III (+)/PCNA (-). Our findings indicate that the majority of differentiating neuronal phenotypes undergoing cytomorphological changes of neuritic development (Nb3), and all neoplastic ganglion cells (Nb4 phenotypes) are PCNA (-), in contrast to actively proliferating, poorly differentiated, tumor cells that are PCNA (+). Although PCNA staining corresponded in part, to beta III (-) blast-like elements (Nb1), a co-expressive pattern of staining for beta III and PCNA/cyclin also was observed in subpopulations of poorly differentiated tumor cells (Nb2), indicating that transformed neuroblasts are capable of expressing differentiation-associated neuronal cytoskeletal proteins while still remaining in the proliferative compartment of the cell cycle. Our observations suggest that only neuritogenesis and acquisition of ganglionic phenotype are significant maturational events in medulloblastomas (indicating entry into the quiescent phase of the cell cycle) and provide further support for the neuronal lineage and differentiation potential of these cerebellar embryonal tumors.

Relaxometry of noncalcified human meningiomas. Correlation with histology and solids content.

RATIONALE AND OBJECTIVES: Resected meningiomas were examined by relaxometry and light microscopy to evaluate the potential of magnetic resonance imaging (MRI) for identifying histologic subtypes and for discriminating among benign, radiation therapy-induced, and malignant meningiomas. METHODS: The magnetic field dependence of 1/T1 of water protons (nuclear magnetic relaxation dispersion [NMRD] profile) and the water content (dry weight) were measured for 67 specimens, and the data were compared with histology. Only noncalcified, nonhemorrhagic meningiomas are reported. RESULTS: No correlations were found between NMRD profiles, dry weight, and any histologic subtype, in contrast to an analogous study of astrocytomas. Rather, meningiomas have a broader variability of dry weight and 1/T1 than related parenchyma but a much narrower range than all grades of astrocytomas. The mean value of 1/T1, at all fields, is slightly higher in meningiomas--and the mean water content about the same--as adult cortical gray matter. CONCLUSION: Meningiomas are frequently isointense with cortex, and histologic subtypes cannot be differentiated at any magnetic field strength by MRI using only T1- or proton density-weighted MRI.

Variation of the magnetic relaxation rate 1/T1 of water protons with magnetic field strength (NMRD profile) of untreated, non-calcified, human astrocytomas: correlation with histology and solids content.

The magnetic relaxation rate 1/T1 of tissue water protons was measured over a wide range of magnetic field strengths (NMRD profile) for 92 fresh surgical specimens of astrocytomas to search for correlations of 1/T1 with tumor histology, as determined by light microscopy, and to assess the diagnostic potential of NMRD profiles for grading astrocytomas. A third goal was to elucidate the molecular determinants of 1/T1. Each specimen was histologically graded and inspected for evidence of mineral deposits (Ca, Fe); its dry weight was determined and expressed in % of original wet weight. To minimize variability not directly related to tumor grade, this initial report is limited to NMRD profiles of 47 non-calcified, non-hemorrhagic, untreated astrocytomas. For these, the mean value of 1/T1 at very low magnetic field strengths was found to increase with increasing grade of malignancy; no clear correlation could be demonstrated at high fields where most imaging is done. The spread of 1/T1 for different grades of malignancy is large, however, and the overlap significant, even at the lowest field, so that astrocytomas can not be graded by NMRD profiles alone. Average 1/T1 and average dry weight increase with grade of malignancy; but the variability of 1/T1 among specimens of the same dry weight is large, indicating that at least one other cellular parameter, not variable in normal tissue, influences 1/T1 strongly. We hypothesize that this parameter reflects changes at the molecular level in size distribution, mobility, or intermolecular interaction of cytoplasmic proteins. Which specific changes are induced by malignant transformation in astrocytomas remains to be investigated.

Pathology of trauma.

The major unifying concept of the effect of trauma on the central nervous system is the application of force to the brain. The mode of delivery of energy and its dissipation result in the varying pathologic manifestations of hemorrhage, contusions, or tears. Topics discussed in this article include inner cerebral trauma, gunshot wounds, contusions and lacerations, hemorrhages, fractures, and spinal cord trauma.

Magnetic field dependence of 1/T1 of human brain tumors. Correlations with histology.

The authors have measured the magnetic field dependence of 1/T1 (nuclear magnetic relaxation dispersion, or NMRD profiles) of water protons of histologically characterized samples of astrocytomas, meningiomas, and lymphomas. The goal was to elucidate the determinants of 1/T1 of brain tumors at the cellular level and, in particular, to search for a possible correlation of the profiles with neoplastic properties, including degree of malignancy. Because of the recently demonstrated contribution of myelin to 1/T1 of white matter, careful histologic analyses were performed to correct for its presence. The range of magnitude of the profiles of differing types and grades of tumors correlates with the range of water content of these tumors; the correlation of water content with cellularity (density of cell nuclei in a histologic preparation), in turn, produces correlations of 1/T1 with tumor type. For all the tumors studied, 1/T1 is proportional to solids content; the constant of proportionality is relatively insensitive to tumor type and, for astrocytomas, grade of malignancy; and is about the same as that of normal gray matter. For low- and intermediate-grade astrocytomas that contain myelin, the myelin-specific contribution to 1/T1 has to be considered to make manifest the underlying correlations, which are best demonstrated at low fields, where the background contribution of water and dissolved oxygen is minimal. At high fields, where most imaging is done, a change in oxygen partial pressure, as for example from ischemia in very malignant tumors, is sufficient to alter 1/T1 significantly, reducing the intrinsic correlation between histology and 1/T1.

Immunoblastic sarcoma of the central nervous system in a patient with lymphomatoid granulomatosis.

A 26-year-old man with lymphomatoid granulomatosis (LYG) was found at postmortem examination to have an immunoblastic sarcoma involving the central nervous system. Residual evidence of LYG was present only in the lungs at autopsy. Studies for intracellular immunoglobulin utilizing the immunoperoxidase technique showed a marked polyclonal reaction in sections of lymph nodes and occasional cells in the cellular central nervous system tumor that stained for intracellular immunoglobulins (IgG, IgM and both kappa and lambda). This case may represent another example of immunoblastic sarcoma occurring in the presence of an abnormal immune state or proliferation.

Primary intracranial Burkitt's lymphoma in an infant.

A case of intracranial Burkitt's lymphoma is reported in a child whose symptoms began at 3 months of age with a definite histologic diagnosis established at 18 months. Serologic studies demonstrated high antibody titers to Epstein-Barr virus (EBV) in the patient and in four out of five members of the immediate family. The patient also demonstrated immunity to antigens derived from African Burkitt's lymphoma cell lines. The autopsy findings strongly support the case for the primary intracranial origin of the neoplasm and a perinatal infection with EBV is probable in this case.

Adult (chronic) GM2 gangliosidosis. Atypical spinocerebellar degeneration in a Jewish sibship.

Two adult Ashkenazi Jewish siblings have had slowly progressive deterioration of gait and posture since early childhood, distal to proximal muscle atrophy, pes cavus, foot drop, spasticity, mild ataxia of limbs and trunk, dystonic features, and dysarthria. Vision and optic fundi are normal, verbal intelligence is stable, and no seizures have occurred. The sister of the patients died at 16 years of age with the same illness. Autopsy showed diffuse neuronal storage, predominating in subcortical areas, consisting of membranocytoplasmic bodies, zebra bodies, and complex lamellar structures. GM2 ganglioside was increased in her brain. Hexosaminidase A was decreased in serum and leukocytes of the living patients, and was in the range for carriers of Tay-Sachs disease in their parents. The disease found in this family represents a new, more indolent variant of GM2 gangliosidosis.

Relapsing juvenile chronic subdural hematoma in adult life.

Two cases of relapsing juvenile chronic subdural hematoma with late relapse in adult life are presented and the literature reviewed. Both patients contracted subdural hematoma early in life; its persistence resulted in characteristic skull deformitites. The patients led an asymptomatic life until a second head trauma caused rebleeding into the old hematoma sac with recurring symptoms and signs. The source of rebleeding is the outer subdural membrane. Radiographic features vary, depending on the location and size of the subdural hematoma. The significance of localized thickening of the cranium is stressed in refining the differential diagnosis.

Progressive demyelination and reparative phenomena in chronic experimental allergic encephalomyelitis.

Chronic experimental allergic encephalomyelitis (EAE), produced in inbred guinea pigs given a single inoculation during the juvenile period with isologous spinal cord in complete Freund's adjuvant, has been studied by light and electron microscopy. Most animals showed a delayed onset of nurologic signs from 12 to 68 weeks post-inoculation (PI), while several were asymptomatic up to 74 weeks PI. Two animals showed a relapsing clinical course. Examination of the spinal cords of all animals revealed chronic demyelination, remyelination, and recent demyelination. Marked perivascular inflammation, including plasma cells, was seen within demyelinated plaques. The usual type of central nervous system (CNS) remyelination was documented but in addition, remyelination of CNS axons by invading Schwann cells was noted. This Schwann cell invasion, not previously seen in EAE, was predominantly in the area of the root entry zone, and occasionally involved extensive areas of the dorsal or ventral horns. The extent of Schwann cell invasion, as well as the usual CNS-type remyelination, demonstrates the reparative capacity of the CNS. The recurrent clinical and morphologic changes in these long-term animals provides further evidence that this model of chronic EAE has many features reminiscent of multiple sclerosis. The underlying immunologic mechanisms responsible for the recurrent disease in these animals are unknown. The presence of plasma cells in the inflammatory exudates might suggest a role for B cells in these chronic animals. The possibility of an intermittent release of loculated adjuvant/antigen accounting for the recurrent disease was considered.

Peroxisomal and mitochondrial defects in the cerebro-hepato-renal syndrome.

The cerebro-hepato-renal syndrome is a rare familial malady with cerebral, renal, and skeletal abnormalities, severe hypotonia, cirrhosis, iron and lipid storage, and death within 6 months. Correlated electron microscopic, histochemical, and biochemical studies demonstrate defects in two oxidative organelles. Peroxisomes cannot be found in hepatocytes and renal proximal tubules. In hepatocytes and cortical astrocytes, mitochondria are distorted in their appearance and glycogen stores are increased. Oxygen consumnption of brain and liver mitochondrial preparations with succinate and with substrates reducing nicotinamide adenine dinucleotide is markedly diminished, but the consumption is normal with ascorbate and tetramethylphenylenediamine, which suggests a defect in electron transport prior to the cytochromes. Histochemical studies of mitochondrial oxidation point to a defect between the succinate dehydrogenase flavoprotein and coenzyme Q, possibly in the region of nonheme iron protein.

Intellectual deficit associated with transplacentally induced microcephaly in the rat.

Fischer rats injected with methylazoxymethanol late in pregnancy produce young with considerably reduced cerebral hemispheres. They appear normal otherwise. As adults these animals make many more errors in the Hebb-Williams maze than do control animals.