Modelling convection-enhanced delivery in normal and oedematous brain.

Convection-enhanced delivery (CED) could have clinical applications in the delivery of neuroprotective agents in brain injury states, such as ischaemic stroke. For CED to be safe and effective, a physician must have accurate knowledge of how concentration distributions will be affected by catheter location, flow rate and other similar parameters. In most clinical applications of CED, brain microstructures will be altered by pathological injury processes. Ischaemic stroke and other acute brain injury states are complicated by formation of cytotoxic oedema, in which cellular swelling decreases the fractional volume of the extracellular space (ECS). Such changes would be expected to significantly alter the distribution of neuroprotective agents delivered by CED. Quantitative characterization of these changes will help confirm this prediction and assist in efforts to model the distribution of therapeutic agents. Three-dimensional computational models based on a Nodal Point Integration (NPI) scheme were developed to model infusions in normal brain and brain with cytotoxic oedema. These models were compared to experimental data in which CED was studied in normal brain and in a middle cerebral artery (MCA) occlusion model of cytotoxic oedema. The computational models predicted concentration distributions with reasonable accuracy.

Absorbed radiation dose of the female breast during diagnostic multidetector chest CT and dose reduction with a tungsten-antimony composite breast shield: preliminary results.

AIM: To determine the absorbed radiation dose to the female breast during chest computed tomography (CT), and whether a custom-designed breast shield can reduce that dose. MATERIALS AND METHODS: Bilateral breast phantoms were combined with an anthropomorphic torso phantom. Each breast phantom contained 20 thermoluminescent dosimeter (TLD) cavities. Eight cavities were used per phantom. Absorbed radiation was measured using TLD 100 s. Three-stacked TLDs comprised a set. Three sets of three TLDs were positioned at eight designated locations and three depths (surface; 1 cm; 4 cm). One set of three TLDs was positioned at eight additional designations, 1cm deep. Each breast was divided anatomically into quadrants. In total, 32 TLD sets/96 TLDs were deployed. The breast-torso phantom was consecutively imaged using a 16-detector array CT machine. Subsequently, 32 new TLD sets were similarly placed, the phantom re-imaged in a likewise manner, but with the application of a tungsten-antimony composite breast shield. TLD readings were averaged and calculated. RESULTS: Average absorbed radiation doses for unshielded right and left breast phantoms ranged from 13.83-19.36 mGy, and 14-20.47 mGy, respectively. The absorbed dose in the shielded right and left breast was reduced to 6.64-8.12 mGy, and 6.7-8.03 mGy, respectively. Average absorbed radiation doses based on the depth for the unshielded breasts ranged from 15.4-18.3 mGy. Shielding reduced this dose to 7-7.9 mGy. Unshielded absorbed radiation doses based on anatomic quadrants ranged from 17.5-18.9 mGy. Shielding reduced this dose to 7-7.5 mGy. CONCLUSIONS: The average absorbed radiation dose to the unshielded female breast phantom is approximately 14-20 mGy. An externally applied shield can reduce this absorbed dose by 56-61%.

A controlled phantom study of a noise equalization algorithm for detecting microcalcifications in digital mammograms.

We report on some extensions and further developments of a well-known microcalcification detection algorithm based on adaptive noise equalization. Tissue equivalent phantom images with and without labeled microcalcifications were subjected to this algorithm, and analyses of results revealed some shortcomings in the approach. Particularly, it was observed that the method of estimating the width of distributions in the feature space was based on assumptions which resulted in the loss of similarity preservation characteristics. A modification involving a change of estimator statistic was made, and the modified approach was tested on the same phantom images. Other modifications for improving detectability such as downsampling and use of alternate local contrast filters were also tested. The results indicate that these modifications yield improvements in detectability, while extending the generality of the approach. Extensions to real mammograms and further directions of research are discussed.

Contribution of edema and cerebral blood volume to traumatic brain swelling in head-injured patients.

OBJECT: The pathogenesis of traumatic brain swelling remains unclear. The generally held view is that brain swelling is caused primarily by vascular engorgement and that edema plays a relatively minor role in the swelling process. The goal of this study was to examine the roles of cerebral blood volume (CBV) and edema in traumatic brain swelling. METHODS: Both brain-tissue water and CBV were measured in 76 head-injured patients, and the relative contribution of edema and blood to total brain swelling was determined. Comparable measures of brain-tissue water were obtained in 30 healthy volunteers and CBV in seven volunteers. Brain edema was measured using magnetic resonance imaging, implementing a new technique for accurate measurement of total tissue water. Measurements of CBV in a subgroup of 31 head-injured patients were based on consecutive measures of cerebral blood flow (CBF) obtained using stable xenon and calculation of mean transit time by dynamic computerized tomography scanning after a rapid bolus injection of iodinated contrast material. The mean (+/- standard deviation) percentage of swelling due to water was 9.37+/-8.7%, whereas that due to blood was -0.8+/-1.32%. CONCLUSIONS: The results of this study showed that brain edema is the major fluid component contributing to traumatic brain swelling. Moreover, CBV is reduced in proportion to CBF reduction following severe brain injury.

Comparison of NAA measures by MRS and HPLC.

This work investigates the accuracy of an in vivo estimation of absolute N-acetyl aspartate (NAA) concentrations by magnetic resonance spectroscopy (MRS) using cerebral water as an internal reference standard. Single-voxel, proton spectroscopy was carried out in two groups of rats (normal and diffuse head injury), using a PRESS sequence with TR = 3 s, TE = 135 ms. Fully relaxed water spectra and water-suppressed proton spectra were obtained from a 7 x 5 x 5 mm3 volume of tissue. MRI-based brain water content measurements were also performed. Following MRS, HPLC determinations of NAA were carried out. In the normal rats the MRS yielded 10.98 +/- 0.83 mmol/kg w.w. vs 10.76 +/- 0.76 for HPLC with a mean absolute difference of 0.8. In the injured rats the corresponding results were 9.41 +/- 1.78 (MRS) and 8.16 +/- 0.77 (HPLC) with a mean absolute difference of 1.66. The in vivo absolute method accurately documented the temporal NAA changes compared to the NAA/Cr approach.

Use of magnetic resonance imaging for in vivo measurements of water content in human brain: method and normal values.

OBJECT: The authors present a quantitative in vivo magnetic resonance (MR) imaging method and propose its use for the accurate assessment of brain water in humans. METHODS: With this technique, a pure T1-weighted image of a selected brain slice in a patient is generated, and the image is subsequently converted to a pure water image by means of an equation derived from a tissue relaxation model. The image intensity in the resulting water map directly yields absolute measures of water expressed in grams of water per gram of tissue at a given anatomical location. The method has been validated previously in a series of phantom experiments and in an infusion model of brain edema in cats. In this report, the authors evaluate the method by using samples of tissue harvested from patients who underwent surgery for brain tumor removal and apply the technique to a series of normal volunteers, providing average regional brain water content (f(w)) values for a range of tissues. Application of the method in pathological conditions such as head trauma, tumor, and hydrocephalus allows quantification of regional or global increases in f(w) that result from edema. CONCLUSIONS: It is now possible to obtain accurate brain water measurements with the anatomical resolution of MR imaging. This permits monitoring of the development and resolution of edema in a variety of clinical circumstances, thus enhancing understanding of the underlying pathophysiological processes.

Quality assurance in mammography: artifact analysis.

Evaluation of mammograms for artifacts is essential for mammographic quality assurance. A variety of mammographic artifacts (i.e., variations in mammographic density not caused by true attenuation differences) can occur and can create pseudolesions or mask true abnormalities. Many artifacts are readily identified, whereas others present a true diagnostic challenge. Factors that create artifacts may be related to the processor (eg, static, dirt or excessive developer buildup on the rollers, excessive roller pressure, damp film, scrapes and scratches, incomplete fixing, power failure, contaminated developer), the technologist (eg, improper film handling and loading, improper use of the mammography unit and related equipment, positioning and darkroom errors), the mammography unit (eg, failure of the collimation mirror to rotate, grid inhomogeneity, failure of the reciprocating grid to move, material in the tube housing, compression failure, improper alignment of the compression paddle with the Bucky tray, defective compression paddle), or the patient (e.g., motion, superimposed objects or substances [jewelry, body parts, clothing, hair, implanted medical devices, foreign bodies, substances on the skin]). Familiarity with the broad range of artifacts and the measures required to eliminate them is vital. Careful attention to darkroom cleanliness, care in film handling, regularly scheduled processor maintenance and chemical replenishment, daily quality assurance activities, and careful attention to detail during patient positioning and mammography can reduce or eliminate most mammographic artifacts.

Regional cerebral blood volume after severe head injury in patients with regional cerebral ischemia.

OBJECTIVE: Recent early cerebral blood flow (CBF) studies in cases of severe head injury have revealed ischemia in a substantial number of patients with a variety of computed tomographically demonstrated diagnoses. The underlying derangements causing this early ischemia are unknown, but cerebral blood volume (CBV) measurements might offer some insight into this pathological abnormality. METHODS: For this purpose, stable xenon-enhanced computed tomography was used for assessment of CBF, and a dynamic computed tomographic imaging technique was used for determining CBV. Based on the occurrence of regional ischemia (CBF < 20 ml/100 g/min), seven patients with varying anatomic lesions revealed by computed tomography were identified for comparison between CBF and CBV in ischemic and nonischemic areas. RESULTS: Both CBF (15+/-4.3 versus 34+/-11 g/min, P < 0.002) and CBV (2.5+/-1.0 versus 4.9+/-1.9 ml/100 g) exhibited significantly lower values in the ischemic zones than in the nonischemic zones (means+/-standard deviations). Among 26 patients with or without ischemia observed during their initial follow-up studies, which were conducted between Days 2 and 8, all patients showed CBF and CBV values within the low-normal range. CONCLUSION: These data evidently support the suggestion that compromise of the microvasculature is the cause of early ischemia, rather than vasospasm of the larger conductance vessels.

Correlations between brain tissue oxygen tension, carbon dioxide tension, pH, and cerebral blood flow--a better way of monitoring the severely injured brain?

BACKGROUND: The ideal method for monitoring the acutely injured brain would measure substrate delivery and brain function continuously, quantitatively, and sensitively. We have tested the hypothesis that brain PO2, pCO2, and pH, which can now be measured continuously using a single sensor, are valid indicators of regional cerebral blood flow (CBF) and oxidative metabolism, by measuring its product, brain pCO2. METHODS: Twenty-five patients (Glasgow Coma Score < or = 8) were studied. A Clark electrode, combined with a fiber optic system (Paratrend 7, Biomedical Sensors, Malvern, PA) was used to measure intraparenchymal brain PO2, pCO2, and pH. Data were averaged over a 1-h period before and after CBF studies. Regional CBF was measured around the probe, using stable xenon computed tomography. Regression analyses and Spearman Rank tests were used for data analysis. RESULTS: Regional CBF and mean brain PO2 were strongly correlated (r=0.74, p=0.0001). CBF values < 18 mL/100 g/min were all accompanied by brain PO2 < or = 26 mm Hg. The four patients with a brain PO2 < 18 mm Hg died. Brain pCO2 and pH, however, were not correlated with CBF (r=0.36, p=0.24 and r=0.30, p=0.43, respectively). CONCLUSIONS: Until recently, substrate supply to the severely injured brain could only be intermittently estimated by measuring CBF. The excellent intra-regional correlation between CBF and brain pO2, suggests that this method does allow continuous monitoring of true substrate delivery, and offers the prospect that measures to increase O2 delivery (e.g., increasing CBF, CPP, perfluorocarbons etc.) can be reliably tested by brain PO2 monitoring.

A new method for quantitative regional cerebral blood volume measurements using computed tomography.

BACKGROUND AND PURPOSE: Knowledge of cerebral blood volume (CBV) is invaluable in identifying the primary cause of brain swelling in patients with stroke or severe head injury, and it might also help in clinical decision making in patients thought to have hemodynamic transient ischemic attacks (TIAs). This investigation is concerned with the development and clinical application of a new method for quantitative regional CBV measurements. METHODS: The technique is based on consecutive measurements of cerebral blood flow (CBF) by xenon/CT and tissue mean transit time (MTT) by dynamic CT after a rapid iodinated contrast bolus injection. CBV maps are produced by multiplication of the CBF and MTT maps in accordance with the Central Volume Principle: CBV = CBF x MTT. The method is rapid and easily implemented on CT scanners with the xenon/CBF capability. It yields CBV values expressed in milliliters of blood per 100 grams of tissue. RESULTS: The method was validated under controlled physiological conditions causing changes that were determined both with our technique and from pressure-volume index (PVI) measurements. The two independent estimates of CBV changes were in agreement within 15%. CBV measurements using this method were carried out in normal volunteers to establish baseline values and to compare with values using the ratio-of-areas method for calculating both CBF and CBV from the dynamic study alone. Average CBV was 5.3 mL/100 g. The method was also applied in 71 patients with severe head injuries and in 1 patient with hemodynamic TIAs. CONCLUSIONS: The primary conclusions from this study were (1) the proposed method for measuring CBV accurately determines changes in CBV; (2) the MTT x CBF determinations are in agreement with the ratio-of-areas method for CBV measurements in normal volunteers and are consistent with other methods reported in the literature; (3) MTTs are significantly prolonged early after severe head injury, which when combined with the finding of decreased CBF and increased arteriovenous difference of oxygen indicates increased cerebrovascular resistance due to narrowing of the microcirculation consistent with the presence of early ischemia; and (4) CBV in the patient with TIAs was increased in the hemisphere with the occluded internal carotid artery, indicating compensatory vasodilation and probable hemodynamic cause.

Investigation of a new light imaging technique to detect incipient caries in teeth.

At the present time dental X-rays are the best method to locate carious lesions, however, small lesions can be detected only with difficulty. Even though investigations in the past have shown that light imaging systems are more sensitive to small lesions than X-rays it is difficult to determine the characteristics of these lesions with any of these systems. We developed a new light imaging technique that makes it much easier to determine the size and depth of these lesions on most areas of the teeth even though modifications on the present setup will still be necessary to detect them as easily on occlusal surfaces. This technique is based on raster scans of the teeth with narrow collimated light beams. The results of this investigation show that the areas ( greater than 0.1 mm 2) of small incipient lesions can be measured and their depths estimated.

Increased spatial resolution in transillumination using collimated light.

In traditional transillumination of the breast (diaphanography), the abundance of diffuse light resulting from the use of extended noncollimated sources reduces the visibility of deep seated lesions. A prototype scanning imaging system has been developed to investigate the effectiveness of thin collimated light beams (1.5 mm cross section) synchronized with a similarly collimated detector to increase contrast in lesions normally lost due to the detection of diffuse light. The study demonstrates that detection of opaque 1.5 mm details is possible in phantoms simulating breast tissues 6 mm thick regardless of depth. This is about 10 times better than images obtained on the same samples using present transillumination methods. Furthermore, this study indicates that internal structures (lesions, cysts) in up to 12 mm thick excised breast sections can be visualized by exploiting their frequency-dependent attenuation. This is accomplished by inserting 50 nm interference filters in the input light path, which can be varied in a stepwise manner in the range of 400 nm to 1000 nm. These results demonstrate for the first time that images of lesion-bearing 1 cm or larger tissues can be obtained, thus opening promising possibilities for whole-breast imaging.

Quantitative phase-velocity MR imaging of in-plane laminar flow: effect of fluid velocity, vessel diameter, and slice thickness.

Quantitative MR phase imaging is frequently used to measure spin velocities. A potential difficulty may arise, however, when in-plane phase images are acquired of a vessel carrying laminar flow, for which the fluid velocity profile is parabolic. In that case, depending on the flow velocity (v), the vessel diameter (D), and the chosen MR slice thickness (ST), a spin velocity gradient will be present to some extent within each intraluminal voxel. The resulting intravoxel phase dispersion may be expected to affect the net pixel phase value, and hence compromise the assumed linear correlation between phase shift and velocity. In this study, the effects of alterations of v, D, and ST on the apparent image phase are investigated for the case of laminar flow directed parallel to the sequence read gradient. A theoretical model is developed and the conclusions experimentally tested using a flow phantom. The data demonstrate that when quantitating inplane phase-flow images, significant velocity underestimations may occur when the net flow-induced phase shifts are small and the MR slice thickness is an appreciable fraction of the vessel diameter.

In vivo brain water determination by T1 measurements: effect of total water content, hydration fraction, and field strength.

This work is concerned with the accurate quantification of brain water content under routine clinical conditions. Gelatin solutions of varying water content are first employed as a model of an edematous brain and longitudinal relaxation measurements are performed at proton Larmor frequencies of 5, 41, 63, and 100 MHz. These are followed with in vivo measurements in an experimental animal model of brain edema at 41 MHz. The results underscore the dominant role of total water content W in the relaxation process and verify the expected linearity between 1/T1 and 1/W. A scheme is presented and experimentally verified at 41 MHz for deducing the exact relationship of 1/T1 vs 1/W at any frequency. Knowledge of this relationship along with precise measurements of 1/T1 at a given field strength permits quantitative in vivo measures of brain water content to be obtained with a precision of about 0.01. It is concluded that routine, accurate, and noninvasive brain water measurements are possible by magnetic resonance imaging in a clinical environment.

Intracranial vascular abnormalities: value of MR phase imaging to distinguish thrombus from flowing blood.

The interpretation of conventional spin-echo and gradient-echo MR images of intracranial vascular lesions can be complex and ambiguous owing to variable effects on image intensity caused by flowing blood or thrombus. MR phase images, obtained simultaneously with conventional-magnitude images, are useful for evaluating proton motion (i.e., blood flow), and therefore can simplify the diagnosis of the presence or absence of thrombosis within a vascular structure or lesion. Fourteen patients with a variety of intracranial vascular abnormalities (aneurysms, superior sagittal sinus thrombosis, neoplasms adjacent to venous sinuses, and vascular malformations) were evaluated with conventional MR and phase imaging for the presence of blood flow. The phase images correlated with angiography in all cases. Phase imaging was not necessarily better than conventional spin-echo imaging in all cases, but it simplified the evaluation of thrombus vs blood flow in many. In three of five aneurysms, the phase images were diagnostic for evaluating lumen patency whereas the conventional images were ambiguous. Phase imaging was advantageous for detecting tumor invasion of the venous sinus when venous blood was enhanced by gadopentetate dimeglumine. A laminar flow phantom experiment determined the lower limits of sensitivity of phase imaging to be 0.5 cm/sec in the slice-select and 2.5 cm/sec in the read gradient directions. Phase imaging is a simple, reliable technique that can distinguish thrombosis from flowing blood within intracranial lesions. It is easily performed and adds no additional time to the MR examination.

Model studies of nonsteady flow using magnetic resonance imaging.

A bolus-tracking magnetic resonance imaging (MRI) method has been employed to measure velocity profiles for oscillatory flow with and without a steady flow component as well as pulsatile flow in an axisymmetric tube model. A range of flow conditions within normal physiological limits was tested. The imaged velocity profiles were observed to be generally in accord with theoretical predictions. Instantaneous flow rates calculated from the MR images agreed well with those assessed using an ultrasonic flowmeter. Because MRI is noninvasive and poses few risks to subjects, this technique is potentially useful for studying vascular hemodynamics in vivo.

In vivo characterization of infusion edema by magnetic resonance imaging.

In vivo measurements of relaxation time profiles were carried out in cats using the infusion model of edema. These profiles were correlated with independent gravimetric measurements of brain water. The results indicated that in vivo determinations of water content by MRI are possible with high spatial resolution.

Velocity profiles in stenosed models using magnetic resonance imaging.

A time-of-flight MRI velocity measurement technique is evaluated against corresponding LDV measurements in a constriction tube model over a range of physiologic flow conditions. Results from this study show that MR displacement images can: (1) be obtained within both laminar and turbulent jets (maximum stenotic Re approximately equal to 4,200); (2) measure mean jet velocities up to 172 cm/s, and (3) detect low forward and reverse velocity regions near the tube wall just downstream of the stenosis (0 less than or equal to L/D less than or equal to 2). Regions between the jet termination point and reestablishment of laminar flow (Re greater than 1,500, greater than 1,000 and greater than 110 downstream of 40, 60 and 80% stenosis, respectively) cannot presently be detected by this technique.

Experimental studies for use of magnetic resonance in brain water measurements.

The accurate description and quantification of altered brain water resulting from different pathologic conditions is of critical clinical importance. In this work we determined the influence of total water content, hydration fraction and magnetic field strength on observed proton relaxation rates by means of in vitro and in vitro model studies and developed a scheme for determining water content at any field strength. Equations relating T1 relaxation times and brain water content are derived. This allows a non-invasive measure of brain water to be determined in the clinical setting.

Stable xenon versus radiolabeled microsphere cerebral blood flow measurements in baboons.

Regional cerebral blood flow was simultaneously determined using the stable xenon computed tomographic and the radioactive microsphere techniques over a wide range of blood flow rates (less than 10-greater than 300 ml/100 g/min) in 12 baboons under conditions of normocapnia, hypocapnia, and hypercapnia. A total of 31 pairs of determinations were made. After anesthetic and surgical preparation of the baboons, cerebral blood flow was repeatedly determined using the stable xenon technique during saturation with 50% xenon in oxygen. Concurrently, cerebral blood flow was determined before and during xenon administration using 15-microns microspheres. In Group 1 (n = 7), xenon and microsphere determinations were made repeatedly during normocapnia. In Group 2 (n = 5), cerebral blood flow was determined using both techniques in each baboon during hypocapnia (PaCO2 = 20 mm Hg), normocapnia (PaCO2 = 40 mm Hg), and hypercapnia (PaCO2 = 60 mm Hg). Xenon and microsphere values in Group 1 were significantly correlated (r = 0.69, p less than 0.01). In Group 2, values from both techniques also correlated closely across all levels of PaCO2 (r = 0.92, p less than 0.001). No significant differences existed between the slopes or y intercepts of the regression lines for either group and the line of identity. Our data indicate that the stable xenon technique yields cerebral blood flow values that correlate well with values determined using radioactive microspheres across a wide range of cerebral blood flow rates.