"Colossal" breakthrough: the callosal puncture as a precursor to third ventriculostomy.

BACKGROUND: In 1908, Anton and von Bramann proposed the Balkenstich method, a corpus callosum puncture which created a communication between the ventricle and subarachnoid space. This method offered the benefit of providing continuous CSF diversion without the implantation of cannula or other shunting devices, yet it received only slight reference in the literature of the time. It remained a novel and perhaps underutilized approach at the time Cushing began expanding his neurosurgical practice at the Johns Hopkins Hospital. MATERIALS AND METHODS: Following IRB approval, and through the courtesy of the Alan Mason Chesney Archives, the surgical records of the Johns Hopkins Hospital for the period 1896-1912 were reviewed. Patients operated upon by Harvey Cushing were selected. RESULTS: 7 patients underwent puncture of the corpus callosum for treatment of hydrocephalus. 6 patients were treated for obstructive hydrocephalus secondary to presumed intracranial lesions. 1 patient was treated for congenital hydrocephalus. CONCLUSION: The series reported here documents Cushing's early use of the corpus callosum puncture to divert CSF in patients with obstructive hydrocephalus secondary to intracranial tumors, as well as an attempt to use the procedure in a pediatric patient with congenital hydrocephalus. Notably, 3 patients developed new onset left-sided weakness post-operatively, possibly due to retraction injury upon the supplementary motor intra-operative manipulations.

Innate immune responses in viral encephalitis.

The innate immune system is multifaceted, comprised of preformed factors, cells, and many proteins and lipid mediators produced by those cells. In the CNS these are critical in initiation and amplification of the inflammatory response and in the subsequent elicitation of the specific T cell response to viral encephalitis. Cells that are resident in brain parenchyma and peripheral cells that are recruited both play key roles in the hosts's responses. Unlike the peripheral compartments, in the CNS, non-cytolytic means of eliminating viral infections have been critical, since, in contrast to columnar epithelial cells, neurons are non-renewing. When the innate immune responses are inefficient or absent in viral encephalitis, pathology is more likely. Much more work remains to elucidate all of the critical cells and their mediators, as well as to develop new therapies for infections of the CNS.

Combined diffusion-weighted and perfusion-weighted flow heterogeneity magnetic resonance imaging in acute stroke.

BACKGROUND AND PURPOSE: The heterogeneity of microvascular flows is known to be an important determinant of the efficacy of oxygen delivery to tissue. Studies in animals have demonstrated decreased flow heterogeneity (FH) in states of decreased perfusion pressure. The purpose of the present study was to assess microvascular FH changes in acute stroke with use of a novel perfusion-weighted MRI technique and to evaluate the ability of combined diffusion-weighted MRI and FH measurements to predict final infarct size. METHODS: Cerebral blood flow, FH, and plasma mean transit time (MTT) were measured in 11 patients who presented with acute (<12 hours after symptom onset) stroke. Final infarct size was determined with follow-up MRI or CT scanning. RESULTS: In normal brain tissue, the distribution of relative flows was markedly skewed toward high capillary flow velocities. Within regions of decreased cerebral blood flow, plasma MTT was prolonged. Furthermore, subregions were identified with significant loss of the high-flow component of the flow distribution, thereby causing increased homogeneity of flow velocities. In parametric maps that quantify the acute deviation of FH from that of normal tissue, areas of extreme homogenization of capillary flows predicted final infarct size on follow-up scans of 10 of 11 patients. CONCLUSIONS: Flow heterogeneity and MTT can be rapidly assessed as part of a routine clinical MR examination and may provide a tool for planning of individual stroke treatment, as well as in targeting and evaluation of emerging therapeutic strategies.

Modeling cerebral blood flow and flow heterogeneity from magnetic resonance residue data.

Existing model-free approaches to determine cerebral blood flow by external residue detection show a marked dependence of flow estimates on tracer arrival delays and dispersion. In theory, this dependence can be circumvented by applying a specific model of vascular transport and tissue flow heterogeneity. The authors present a method to determine flow heterogeneity by magnetic resonance residue detection of a plasma marker. Probability density functions of relative flows measured in six healthy volunteers were similar among tissue types and volunteers, and were in qualitative agreement with literature measurements of capillary red blood cell and plasma velocities. Combining the measured flow distribution with a model of vascular transport yielded excellent model fits to experimental residue data. Fitted gray-to-white flow-rate ratios were in good agreement with PET literature values, as well as a model-free singular value decomposition (SVD) method in the same subjects. The vascular model was found somewhat sensitive to data noise, but showed far less dependence on vascular delay and dispersion than the model-free SVD approach.

Multinuclear solid-state three-dimensional MRI of bone and synthetic calcium phosphates.

Multinuclear three-dimensional solid-state MRI of bone, tooth, and synthetic calcium phosphates is demonstrated in vitro and in vivo with a projection reconstruction technique based on acquisition of free induction decays in the presence of fixed amplitude magnetic field gradients. Phosphorus-31 solid-state MRI provides direct images of the calcium phosphate constituents of bone substance and is a quantitative measurement of the true volumetric bone mineral density of the bone. Proton solid-state MRI shows the density of bone matrix including its organic constituents, which consist principally of collagen. These solid-state MRI methods promise to yield a biological picture of bone richer in information concerning the bone composition and short range-crystalline order than the fluid-state images provided by conventional proton MRI or the density images produced by radiologic imaging techniques. Three-dimensional solid-state projection reconstruction MRI should be readily adaptable to both human clinical use and nonmedical applications for a variety of solids in materials science.

Evaluation of bone mineral density using three-dimensional solid state phosphorus-31 NMR projection imaging.

A solid state magnetic resonance imaging technique is used to measure true three-dimensional mineral density of synthetic hydroxyapatite phantoms and specimens of bone ex vivo. The phosphorus-31 free induction decay at 2.0 T magnetic field strength is sampled following application of a short, hard radiofrequency excitation pulse in the presence of a fixed amplitude magnetic field gradient. Multiple gradient directions covering the unit sphere are used in an efficient spherical polar to Cartesian interpolation and Fourier transform projection reconstruction scheme to image the three-dimensional distribution of phosphorus within the specimen. Using 3-6 Gauss/cm magnetic field gradients, a spatial resolution of 0.2 cm over a field of view of 10 cm is achieved in an imaging time of 20-35 minutes. Comparison of solid state magnetic resonance imaging with dual energy X-ray absorptiometry (DXA), gravimetric analysis, and chemical analysis of calcium and phosphorus demonstrates good quantitative accuracy. Direct measurement of bone mineral by solid state magnetic resonance opens up the possibility of imaging variations in mineral composition as well as density. Advantages of the solid state magnetic resonance technique include avoidance of ionizing radiation; direct measurement of a constituent of the mineral without reliance on assumptions about, or models of, tissue composition; the absence of shielding, beam hardening, or multiple scattering artifacts; and its three-dimensional character. Disadvantages include longer measurement times and lower spatial resolution than DXA and computed tomography, and the inability to scan large areas of the body in a single measurement, although spatial resolution is sufficient to resolve cortical from trabecular bone for the purpose of measuring bone mineral density.

Imaging perfusion deficits in ischemic heart disease with susceptibility-enhanced T2-weighted MRI: preliminary human studies.

AIM: This feasibility study explores relative myocardial perfusion characterization with an investigational T2/T2 contrast agent. METHODS: Dysprosium-DTPA bis (methylamide) was administered peripherally in six patients with thallium defects. Rest and stress multi-section, gated, T2-weighted images were acquired with a 1.5 T echo-planar imager. Change in transverse relaxation rate was calculated in four segments for each subject. RESULTS: Magnetic resonance (MR) identified five of five instances of ischemia or infarction, at a dose of agent (0.25 mmol/kg) that was comparable to that currently used with clinically approved gadolinium agents. Injection at twice this dose resulted in saturation of the signal change, and the one ischemic segment corresponding to the higher dose was not identified by MR. MR was negative in two segments which, on final diagnosis, were determined to manifest thallium attenuation artifact. CONCLUSION: MR perfusion imaging with high susceptibility agents has the potential to characterize myocardial perfusion deficits.

Dynamic liver imaging with iron oxide agents: effects of size and biodistribution on contrast.

In vivo effective relaxation rates in normal rat liver were evaluated for four dextran coated iron oxide agents: monocrystalline iron oxide nanocolloid (MION) with a mean particle diameter of 3.9 nm, a polycrystalline agent (PION) with a larger mean diameter of 12 nm, and these two agents labeled with the asialofetuin (ASF) protein for high hepatocytic receptor binding affinity (MION-ASF and PION-ASF). Using echo planar imaging at 2 Tesla, dose response was measured with measured with high temporal resolution for 3 h after injection of agent, and by comparing with relaxivities in vitro and in brain, dominant in vivo contrast phenomena were elucidated. While transverse relaxivity for PION-ASF exceeded that for MION-ASF by almost a factor of 2 in solution, relaxation rates in vivo became equivalent. Liver relaxation using non-ASF agents was consistent with rapid water exchange between vascular and extravascular compartments, which dominated relaxation as a result of agent accumulation in Kupffer cells.

The MRT1 based perfusion model.

There are a number of theoretical and practical questions one needs to consider to understand and optimize contrast to noise of the versatile T1 based perfusion model. We made an evaluation of the several popular T1 based methods currently applied to measure flow and flow change.

Improving MR quantification of regional blood volume with intravascular T1 contrast agents: accuracy, precision, and water exchange.

The goal of this work was to develop a comprehensive understanding of the relationship between vascular proton exchange rates and the accuracy and precision of tissue blood volume estimates using intravascular T1 contrast agents. Using computer simulations, the effects of vascular proton exchange and experimental pulse sequence parameters on measurement accuracy were quantified. T1 and signal measurements made in a rat model implanted with R3230 mammary adenocarcinoma tumors demonstrated that the theoretical findings are biologically relevant; data demonstrated that over-simplified exchange models may result in measures of tumor, muscle, and liver blood volume fractions that depend on experimental parameters such as the vascular contrast concentration. As a solution to the measurement of blood volume in tissues with exchange that is unknown, methods that minimize exchange rate dependence were examined. Simulations that estimated both the accuracy and precision of such methods indicated that both the inversion recovery and the transverse-spoiled gradient echo methods using a "no-exchange" model provide the best trade-off between accuracy and precision.

High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: Mathematical approach and statistical analysis.

The authors review the theoretical basis of determination of cerebral blood flow (CBF) using dynamic measurements of nondiffusible contrast agents, and demonstrate how parametric and nonparametric deconvolution techniques can be modified for the special requirements of CBF determination using dynamic MRI. Using Monte Carlo modeling, the use of simple, analytical residue models is shown to introduce large errors in flow estimates when actual, underlying vascular characteristics are not sufficiently described by the chosen function. The determination of the shape of the residue function on a regional basis is shown to be possible only at high signal-to-noise ratio. Comparison of several nonparametric deconvolution techniques showed that a nonparametric deconvolution technique (singular value decomposition) allows estimation of flow relatively independent of underlying vascular structure and volume even at low signal-to-noise ratio associated with pixel-by-pixel deconvolution.

MR perfusion studies with T1-weighted echo planar imaging.

The T1 perfusion model has worked well in brain functional studies where flow changes are measured. Using selective and nonselective inversion pulses, a new method has been developed to study steady-state brain blood flow. The authors obtained flow-sensitive images using selective inversion and flow-insensitive images using nonselective inversion. Subtraction of flow-insensitive images from flow-sensitive images gave us flow-weighted images with good gray-white flow contrast in cortical gray matter as well as in the thalamus and basal ganglia. Fitting T1s of flow-insensitive and flow-sensitive images allowed us to obtain preliminary results of brain blood flow maps. Two specific problems can seriously affect the accuracy of the brain blood flow values and the gray-white flow contrast of brain blood flow maps. These are the problems of the partial volume effect of CSF and gray matter, and the difference between blood T1 and white matter T1. The authors discuss in detail the character of these problems and present a number of approaches to manage such problems.

Intramural mechanics in hypertrophic cardiomyopathy: functional mapping with strain-rate MR imaging.

PURPOSE: To characterize systolic and diastolic intramural mechanics in hypertrophic cardiomyopathy (HCM) with a new metric of contractile activity. MATERIALS AND METHODS: Eleven healthy subjects and eight patients with HCM underwent velocity-encoded echo-planar magnetic resonance (MR) imaging (6-8-frame gated breath-hold movies, 3 x 3-mm resolution). A scalar strain rate (SR) parameter was compared with wall thickness and symptoms. RESULTS: The normal pattern of SR included regional uniformity, a monotonically increasing subepicardial to subendocardial gradient, and minimum transmural shear rate. In HCM, heterogeneity of SRs increased in diastole. Regional diastolic SR correlated with regional wall thickness (r = .785, P = .0001). Interobserver global SR assignment agreed in seven of eight patients. All four patients with New York Heart Association class 1 disease had a low global SR deficit score, whereas three of four patients with class 2 or 3 disease had a high SR deficit score (Spearman r = .775, P = .187). CONCLUSION: SR characterization may provide an objective measure of disease course in HCM.

Magnetic resonance imaging mapping of brain function. Human visual cortex.

Magnetic resonance imaging (MRI) studies of human brain activity are described. Task-induced changes in brain cognitive state were measured using high-speed MRI techniques sensitive to changes in cerebral blood volume (CBV), blood flow (CBF), and blood oxygenation. These techniques were used to generate the first functional MRI maps of human task activation, by using a visual stimulus paradigm. The methodology of MRI brain mapping and results from the investigation of the functional organization and frequency response of human primary visual cortex (V1) are presented.

Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation.

Neuronal activity causes local changes in cerebral blood flow, blood volume, and blood oxygenation. Magnetic resonance imaging (MRI) techniques sensitive to changes in cerebral blood flow and blood oxygenation were developed by high-speed echo planar imaging. These techniques were used to obtain completely noninvasive tomographic maps of human brain activity, by using visual and motor stimulus paradigms. Changes in blood oxygenation were detected by using a gradient echo (GE) imaging sequence sensitive to the paramagnetic state of deoxygenated hemoglobin. Blood flow changes were evaluated by a spin-echo inversion recovery (IR), tissue relaxation parameter T1-sensitive pulse sequence. A series of images were acquired continuously with the same imaging pulse sequence (either GE or IR) during task activation. Cine display of subtraction images (activated minus baseline) directly demonstrates activity-induced changes in brain MR signal observed at a temporal resolution of seconds. During 8-Hz patterned-flash photic stimulation, a significant increase in signal intensity (paired t test; P less than 0.001) of 1.8% +/- 0.8% (GE) and 1.8% +/- 0.9% (IR) was observed in the primary visual cortex (V1) of seven normal volunteers. The mean rise-time constant of the signal change was 4.4 +/- 2.2 s for the GE images and 8.9 +/- 2.8 s for the IR images. The stimulation frequency dependence of visual activation agrees with previous positron emission tomography observations, with the largest MR signal response occurring at 8 Hz. Similar signal changes were observed within the human primary motor cortex (M1) during a hand squeezing task and in animal models of increased blood flow by hypercapnia. By using intrinsic blood-tissue contrast, functional MRI opens a spatial-temporal window onto individual brain physiology.

Proton NMR imaging of cerebral blood flow using H2(17)O.

Cerebral blood flow was quantitatively mapped by monitoring the cerebral washout of H2(17)O using rapid, single-shot proton NMR imaging. H2(17)O acts as a freely diffusible contrast agent for proton imaging via its scalar-coupled term, enhancing T2 relaxation. Measured values for CBF ranged from 29 to 106 ml/min/100 g over a range of arterial pCO2 between 23 and 81 Torr.

Water movement in the rabbit eye.

The intraocular distribution of topically applied D2O was quantified using deuterium nuclear magnetic resonance (NMR) spectroscopy. D2O appeared in all tissues with the highest concentration in the aqueous humor (1.2 M); however, it rapidly dissipated from the eye. Surface coil NMR spectroscopy on D2O-treated eyes in vivo showed that the flow pattern was best described by a single exponential decay plus a constant. This suggests that the D2O flow consisted of a flow component representing vascular circulation (with a flow rate constant of 0.101 min-1), and a reservoir-like component. Topical D2O in conjunction with the surface-coil NMR technique can be used to examine the movement of water in the anterior segment of the living eye.

Computer versus visual analysis of exercise thallium-201 images: a critical appraisal in 325 patients with chest pain.

Although computer-aided analysis of planar thallium images has been previously reported to be superior to visual analysis, a segment-by-segment comparison of all thallium variables (presence of initial defect, presence of redistribution, and presence of abnormal lung:heart thallium ratio) has not been performed with the use of both methods. In the present study, such a comparison was performed to determine which thallium variable(s) are superior, when the computer method is used. In addition, both methods were compared to determine their correlations with the angiographic extent of coronary artery disease (no disease, or one-vessel disease vs multivessel, or left main disease) and the occurrence of future events (cardiac-related death or nonfatal myocardial infarction). Computer-aided analysis was superior to visual analysis (an average of three independent blinded observers) for detection of coronary disease because: (1) it was more specific for detecting initial defects despite having the same sensitivity (89.6% vs 91.0%, p = NS) and (2) it was more sensitive for detecting redistribution in the territory of a stenosed vessel (68% vs 46%, p less than 0.001). However, absolute myocardial clearance of thallium had very poor specificity compared to visually assessed redistribution. Only when segmental clearance was considered abnormal on a relative basis (if it was slower by 98% or more than the fastest clearing segment in the heart) did abnormal clearance achieve the same specificity (99%) and a better sensitivity (60% vs 48%, p less than 0.01) than visual analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative aspects of myocardial perfusion imaging.

Computer quantitation of myocardial perfusion images has enhanced the detection of thallium perfusion abnormalities compared to visual analysis. Computer analysis is more specific than visual analysis for detection of initial defects and more sensitive for detection of redistribution. Computer analysis is equally good for detecting thallium abnormalities in the distribution of the three major coronary arteries. Measurement of absolute clearance of thallium results in an unacceptable high false-positive rate. However, when clearance in a myocardial segment is compared to the fastest clearing segment in the heart, the specificity of clearance improves significantly. Quantitation of lung:heart ratio is very useful. Increased lung:heart ratio reflects exercise induced left ventricular dysfunction and is a strong marker of prognosis. Single photon emission computerized tomography (SPECT) offers the potential of more precisely sizing the risk area. The question of whether this technique offers a significant advantage over planar thallium imaging has to be answered.

Regional variability in the myocardial clearance of thallium-201 and its importance in determining the presence or absence of coronary artery disease.

There are several limitations in using absolute myocardial clearance of thallium-201 for the detection of coronary artery disease. Noncardiac factors such as peak exercise heart rate and blood level of thallium can affect its absolute myocardial clearance. However, because all myocardial segments in a given heart are exposed to the same noncardiac factors, a relative difference in myocardial clearance of thallium between segments could reflect the presence of coronary artery disease. Accordingly, myocardial clearance of thallium was analyzed in 370 patients. Patients in Group I (n = 45) had less than 1% probability of having coronary artery disease, patients in Group II (n = 44) had normal coronary arteries and patients in Group III (n = 281) had coronary artery disease. Although mean myocardial clearance of thallium in 15 myocardial segments in three views in Group I subjects was 3.4 +/- 0.7 hours, the variability between the slowest and fastest clearing segments in the same subject was as much as 98%. This variability was systematic, suggesting technical reasons associated with imaging as the cause of the variability: 78% of the slowest clearing segments were basal whereas 53% of the fastest clearing segments were apical (p less than 0.01). When Group II and III patients were compared based on Group I values, the absolute myocardial clearance of thallium had a sensitivity and specificity of 92 and 16%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)