Quantification of cerebral blood flow by bolus tracking and artery spin tagging methods

This study deals with perfusion quantification in healthy volunteers using two types of dynamic magnetic resonance imaging (MRI) methods. Absolute cerebral blood flow (CBF) measurements were performed in 11 subjects by applying both bolus tracking of exogenous contrast agent and non-invasive arterial spin labeling MRI techniques. Both methods produced CBF images with good tissue contrast and CBF values are in good agreement with literature data. The correlation between cerebral blood volume (CBV) and CBF is also discussed.     

Correlation of regional cerebral blood flow from perfusion MRI and spect in normal subjects

The objective of this study was to determine the relationship in regional cerebral blood flow (rCBF) as measured with perfusion magnetic resonance imaging (pMRI) and single photon emission computer tomography (SPECT). rCBF was determined in 26 healthy subjects with pMRI and SPECT. After co-registration of pMRI with SPECT, rCBF was determined in 10 brain regions relative to the whole slice value. pMRI was evaluated with and without elimination of large vessels. rCBF from pMRI correlates significantly with rCBF from SPECT (r = 0.69 with and r = 0.59 without elimination of large vessels; p < 0.0001 for both). Elimination of large vessels reduced the interindividual variance of the pMRI measurements in most regions. rCBF from pMRI shows good correlation with rCBF from SPECT. Because pMRI is sensitive to flow in large vessels while SPECT is not, elimination of large vessels in pMRI reduces the interindividual variability of pMRI and improves the-correlation between the two methods. pMRI is a reliable noninvasive method for rCBF measurements.     

Superparamagnetic iron oxide particles and positive enhancement for myocardial perfusion studies assessed by subsecond T1-weighted MRI

Superparamagnetic iron oxide particles (SPIOs) are usually referred to as T₂ MR contrast agents, reducing signal intensity (SI) on T₂-weighted MR images (negative enhancement). This study reports the original use of SPIOs as T₁-enhancing contrast agents, primarily assessed in vitro, and then applied to an in vivo investigation of a myocardial perfusion defect. Using a strongly T₁-weighted subsecond MR sequence with SPIOs intravenous (IV) bolus injection, MR imaging of myocardial vascularization after reperfusion was performed, on a dog model of coronary occlusion followed by reperfusion. Immediately after the intravenous bolus injection of 20 μmol/kg of SPIOs, a positive signal intensity enhancement was observed respectively, in the right and left ventricular cavity and in the nonischemic left myocardium. Moreover, compared to normal myocardium, the remaining ischemic myocardial region (anterior wall of the left ventricle) appeared as a lower and delayed SI enhancing area (cold spot). Mean peak SIE in the nonischemic myocardium (posterior wall) was significantly higher than in the ischemic myocardium (anterior wall) (110 ± 23% vs. 74 ± 22%, Mann-Whitney test < 1%, n₁ = 6, n₂ − n₁ = 0, U > 2). In conclusion, the T₁ effect of SPIOs at low dose, during their first intravascular distribution, suggests their potential use as positive markers to investigate the regional myocardial blood flow and some perfusion defects such as the “no-reflow phenomenon”.     

Aspects on the accuracy of cerebral perfusion parameters obtained by dynamic susceptibility contrast MRI: a simulation study

Several studies have indicated that deconvolution based on singular value decomposition (SVD) is a robust concept for retrieval of cerebral blood flow in dynamic susceptibility contrast (DSC) MRI. However, the behavior of the technique under typical experimental conditions has not been completely investigated. In the present study, cerebral perfusion was simulated using different temporal resolutions, different signal-to-noise ratios (S/Ns), different shapes of the arterial input function (AIF), different signal drops, and different cut-off levels in the SVD deconvolution. Using Zierler's area-to-height relationship in combination with the central volume theorem, calculations of regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), and regional mean transit time (rMTT) were accomplished, based on simulated DSC-MRI signal curves corresponding to artery, gray matter (GM), white matter (WM), and ischemic tissue. Gaussian noise was added to the noise-free signal curves to generate different S/Ns. We studied image time intervals of 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 s, as well as different degrees of signal decrease. The singular-value threshold in the SVD procedure and the shape of the AIF were also varied. Increased rCBF was seen when noise was added, especially for rCBF in WM at the larger image time intervals. The rCBF showed large standard deviations using a low threshold value. A prolonged time interval led to a lower absolute value of rCBF both in GM and WM, and a low/broad AIF also underestimated the rCBF. When a larger maximal signal decrease was assumed, smaller standard deviations were observed. No systematic change of the average rCBV was observed with increasing noise or with increasing image time interval. At S/N = 40, a low cut-off value resulted in an rCBF that was closer to the true value. Furthermore, at low S/N it was difficult to differentiate ischemic tissue from WM.     

Improved T(1)-weighted dynamic contrast-enhanced MRI to probe microvascularity and heterogeneity of human glioma

Dynamic contrast-enhanced (DCE) T(1)-weighted magnetic resonance imaging (MRI) is a powerful tool capable of providing quantitative assessment of contrast uptake and characterization of microvascular structure in human gliomas. The kinetics of the bolus injection doped with increasing concentrations of gadopentate dimeglumine (Gd-DTPA) depends on tissue as well as pulse sequence parameters. A simple method is described that overcomes the limitation of relative signal increase measurement and may lead to improved accuracy in quantification of perfusion indices of glioma. Based on an analysis of the contrast behavior of spoiled gradient-recalled echo sequence; a parameter K with arbitrary unit 5.0 is introduced, which provides a better approximation to the differential T(1) relaxation rate. DCE-MRI measurements of relative cerebral blood volume (rCBV) and cerebral blood flow (rCBF) were calculated in 25 patients with brain tumors (15=high-grade glioma, 10=low-grade glioma). The mean rCBV was 6.46 +/- 2.45 in high-grade glioma and 2.89 +/- 1.47 in the low-grade glioma. The rCBF was 3.94 +/- 1.47 in high-grade glioma while 2.25 +/- 0.87 in low-grade glioma. A significant difference in rCBF and rCBV was found between high- and low-grade gliomas. This simple and robust technique reveals the complexity of tumor vasculature and heterogeneity that may aid in therapeutic management especially in nonenhancing high-grade gliomas. We conclude that the precontrast medium steady-state residue parameter K may be useful in improved quantification of perfusion indices in human glioma using T(1)-weighted DCE-MRI.     

The influence of hyperoxia on regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and cerebral blood flow velocity in the middle cerebral artery (CBFVMCA) in human volunteers

Conflicting results reported on the effects of hyperoxia on cerebral hemodynamics have been attributed mainly to methodical and species differences. In the present study contrast-enhanced magnetic resonance imaging (MRI) perfusion measurement was used to analyze the influence of hyperoxia (fraction of inspired oxygen (FiO2) = 1.0) on regional cerebral blood flow (rCBF) and regional cerebral blood volume (rCBV) in awake, normoventilating volunteers (n = 19). Furthermore, the experiment was repeated in 20 volunteers for transcranial Doppler sonography (TCD) measurement of cerebral blood flow velocity in the middle cerebral artery (CBFV(MCA)). When compared to normoxia (FiO2 = 0.21), hyperoxia heterogeneously influenced rCBV (4.95 +/- 0.02 to 12.87 +/- 0.08 mL/100g (FiO2 = 0.21) vs. 4.50 +/- 0.02 to 13.09 +/- 0.09 mL/100g (FiO2 = 1.0). In contrast, hyperoxia diminished rCBF in all regions (68.08 +/- 0.38 to 199.58 +/- 1.58 mL/100g/min (FiO2 = 0.21) vs. 58.63 +/- 0.32 to 175.16 +/- 1.51 mL/100g/min (FiO2 = 1.0)) except in parietal and left frontal gray matter. CBFV(MCA) remained unchanged regardless of the inspired oxygen fraction (62 +/- 9 cm/s (FiO2 = 0.21) vs. 64 +/- 8 cm/s (FiO2 = 1.0)). Finding CBFV(MCA) unchanged during hyperoxia is consistent with the present study's unchanged rCBF in parietal and left frontal gray matter. In these fronto-parietal regions predominantly fed by the middle cerebral artery, the vasoconstrictor effect of oxygen was probably counteracted by increased perfusion of foci of neuronal activity controlling general behavior and arousal.     

Assessment of mitral regurgitation by magnetic resonance imaging

To evaluate the potential of magnetic resonance imaging (MRI) in detection and quantification of mitral regurgitation, 26 pts. with echocardiographically or angiographically documented mitral regurgitation were examined using a 0.5 Tesla superconducting magnet. In each patient a multislice-multiphase study in a sagittal-coronal double angulated projection (four-chamber view equivalent) was performed to assess left and right ventricular volumes, ejection fraction and regurgitant fraction. Additionally a blood flow sensitive cine-study (fast field echo: FFE) was done to visualize direction and area of regurgitant jet. MRI data were compared with quantitative and qualitative assessment of mitral regurgitation by angiography, 2D echocardiography, Doppler sonography and color flow mapping. Using the FFE mode MRI was able to detect the regurgitant jet as a typical signal loss within the left atrium in all patients. The ratio of regurgitant jet area/left atrium area as determined by MRI showed a correlation with a comparable ratio from color Doppler sonography of R = 0.87 (p < 0.001). There was also good agreement in semiquantitative grading of mitral regurgitation between MRI and angiography (R = 0.77, p < 0.001). The determination of left and right ventricular stroke volume allowed the calculation of the regurgitant fraction, which showed a correlation with invasively determined regurgitation fraction of R = 0.84 (p < 0.001). These data provide additional information that MRI may be useful as a noninvasive technique to detect and quantify mitral regurgitation.     

Study of cerebrovascular reserve capacity by magnetic resonance perfusion weighted imaging and photoacoustic imaging

The aim of this work was to assess the feasibility of photoacoustic imaging (PAI) and MR imaging for evaluating the cerebrovascular reserve capacity (CVRC) in animal models. Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHR) were used for MRI. BALB/c mice were used for PAI. MR perfusion weighted imaging (PWI) was performed on a 1.5-T whole-body MR system before and after oral administration of acetazolamide (ACZ). The region of interest (ROI) was chosen in the bilateral frontal lobe for measuring regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and mean transit time (MTT). The vessel diameters of the superficial layer of the cortex were measured by PAI in the resting and ACZ-activated mice. The results showed that there was a statistical difference between the resting and ACZ-activated animals in vessel diameter, rCBV and rCBF values. The increments in rCBV and rCBF of WKY rats between resting and ACZ test states were significantly higher than that of SHR. The pathological findings of small arterial walls and lumen of the brain were also different between WKY and SHR rats. The diameters of blood vessels in the superficial layer of the brain measured by PAI were enlarged after the ACZ tolerance test. This result was also observed in the MRI CBV map, where the signal of the vessel in the superficial layer of the cortex became redder after the ACZ stimulation, suggesting the increase of blood flow. It can be concluded that MR PWI and PAI combined with the ACZ test might be useful in evaluating the CVRC and revealing the pathologic changes in cerebral vessels.     

Hemodynamic investigation of peritumoral impaired blood oxygenation-level dependent cerebrovascular reactivity in patients with diffuse glioma

IntroductionThe presence of peritumorally impaired blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) has been unequivocally demonstrated in patients with diffuse glioma, and may have value to better identify tumor infiltration zone. Since BOLD-CVR does not measure hemodynamic changes directly, we performed additional MR perfusion studies to better characterize the peritumoral hemodynamic environment.MethodsSeventeen patients with WHO grade III and IV diffuse glioma underwent high resolution advanced hemodynamic MR imaging including BOLD-CVR and MR perfusion. The obtained multiparametric hemodynamic factors (i.e., regional cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean transit time (MTT), time-to-peak (TTP) and BOLD-CVR, were analyzed within 10 concentric expanding 3 mm volumes of interest (VOIs) up to 30 mm from the tumor tissue mask.ResultsBOLD-CVR impairment was found within the tumor tissue mask and the peritumoral VOIs up to 21 mm as compared to the contralateral flipped CVR analysis (p<0.05). In the affected hemisphere, we observed positive spatial correlations including all VOIs between BOLD-CVR and rCBV values (r=0.27; p<0.001), rCBF (r=0.42; p<0.001) and a negative correlation between BOLD-CVR and TTP (r=-0.47; p<0.001).ConclusionsPeritumorally impaired BOLD-CVR is associated with concomitant hemodynamic alterations with severity correlating to tumor volume. The distribution of these multiparametric hemodynamic MRI patterns may be considered for future studies characterizing the hemodynamic peritumoral environment, thereby better identifying the extent of tumor infiltration.     

Density profile and flow of miscible fluid with dissimilar constituent masses

A computer simulation model is used to study the density profile and flow of a miscible gaseous fluid mixture consisting of differing constituent masses (m_A=m_B/3) through an open matrix. The density profile is found to decay with the height ∝exp (−m_A(B)h), consistent with the barometric height law. The flux density shows a power-law increase ∝(p_c−p)^μ with μ2.3 at the porosity 1−p above the pore percolation threshold 1−p_c.     

Assessing outcomes for dysphonic patients

This study was designed to evaluate a disease-specific outcome measure for patients with selected voice disorders and to relate this instrument to a standardized quality of life measurement. In addition, the study attempts to document the degree of handicap for dysphonia patients globally, between different vocal pathologies, and in comparison to other chronic diseases. In this prospective, observational study, 260 adult patients evaluated for alterations of voice completed a general quality of life measure (the Medical Outcomes Trust Short Form 36-Item[SF-36]) and a voice-specific instrument (Voice Handicap Index [VHI]) pretreatment.

The highest correlation was between the social functioning score of the SF-36and the total score of the VHI and the physical, emotional, and functional subscales (p < 0.001) of the VHI. Significant correlation was also obtained for the SF-36 domains mental health (p < 0.01), general health (p < 0.01), and role functioning emotional (p < 0.017) with the three VHI domains and the total VHI score. Patients had significantly lower scores than the general U.S. population in five of the eight domains of SF-36. Patients with vocal fold paralysis had the highest level of pretreatment disability as measured on both the VHI and SF-36 among voice patients. The patients with dysphonia had a lower level of physical functioning than the patients with chronic sinusitis (p < 0.01), reflecting a greater handicap. In addition, the dysphonia group had lower levels of social functioning than the angina (p < 0.01) and sciatica (p < 0.01) groups and a lower score for mental health than the angina group (p < 0.01).

The SF-36 correlates with the VHI in the domains of social functioning,mental health, and role functioning emotional. The baseline handicap for voice disorders represents a significant disability even in comparison to conditions such as angina pectoris, sciatica, and chronic sinusitis.     

Correlation between liver iron content and magnetic resonance imaging in rats

Currently, serum ferritin concentration is the best noninvasive estimator of liver iron content. This study investigated the ability of magnetic resonance imaging to determine hepatic iron concentration. Fisher rats were treated with either parenteral iron to increase levels or phlebotomy to lower them and achieved a wide range of liver iron concentrations. Rats were imaged using a clinical whole body scanner at 1.5 Tesla with a 15-cm Helmholtz surface coil and a 23-cm field of view. The ratio of signal intensity of liver to skeletal muscle from images of the live intact rats correlated well with chemically measured iron concentration of the liver (r = −.89, p < .0001, linear regression analysis). Transverse relaxation rates (1/calculated T₂ relaxation times) also correlated with liver iron content (r = .66, p < .0001). The observation of a significant correlation between liver iron content and both signal intensities and T₂ relaxation rates, obtained by magnetic resonance imaging, may have considerable clinical relevance. If adapted to humans, this technique would have obvious applications in the diagnosis and management of diseases associated with iron overload as well as in the investigation of the overall role of iron in various human liver diseases.     

Quantitative perfusion imaging in carotid artery stenosis using dynamic susceptibility contrast-enhanced magnetic resonance imaging

Quantitative, multislice dynamic susceptibility contrast-enhanced MRI perfusion measurements were used to determine the patterns of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and normalized first moment of the tissue deltaR2-time curve (N) in 11 subjects with carotid artery occlusion or stenosis. MTT correlated with degree of carotid stenosis, whereas a range of alterations in CBF and CBV were found presumably reflecting variables degrees of collateral flow. There was no significant correlation between MRI and SPET flow perfusion measurements, with increasing disparity between the two techniques at higher inter-hemispheric flow ratios. The effect of obtaining the arterial input function (AIF) from the middle cerebral artery (MCA) ipsilateral or contralateral to the stenosis was determined. Despite the use of an AIF from the MCA, which is distal to the circle of Willis, and hence the major sources of collateral supply, there was still some extra dispersion of the contrast agent bolus due to differences in arrival time.     

Field-induced parameters of re-entrant magnets and concentrated spin glasses

We have used electron spin resonance measurements to derive the temperature and frequency dependences of the field-induced magnetization [M(T, f)] and anisotropy field [H_an (T)] in a number of amorphous alloys belonging to the series (Fe_pNi_1−p)₇₅P₁₆B₆Al₃. In re-entrant (p > p_c, the critical concentration for ferromagnetism) alloys at hi gh frequencies (f = 35 GHz, field ≈ 12 kOe) M reduces as T^3/2 at high T and as T below ≈ 40 K, the deviation from T^3/2 becoming more marked as p → p⁺_c. For p close to p_c, lowering the frequency first causes the T term to increase and ultimately ( ≈ 4 GHz) changes the variation of M with T to that discovered previously for concentrated spin glasses, namely M is constant at low T and drops linearly at high temperatures. For the re-entrants, the results are interpreted on the basis of a model which invokes an energy gap in the spin-wave spectrum, introduces a non-zero density of states of the gap energy and takes into consideration a low-q cut-off in the spin-wave integral in thelow-T (T) regime.In the concentrated spin glasses [M (0) - M (T)]/ M (0) is well represented by the function [exp (Δ / T) - 1]^-1, where Δ has values close to the corresponding Curie-Weiss temperatures θ_p but much larger than the respective spin glass transition temperatures T_SG. The temperature dependence of H_an is largely given by the function (1 - T/T^*), where T^* is equal to the zero-field freezing temperature for the re-entrants and T_SG for the spin glasses, respectively.     

The two-point correlation function of the one-dimensional matrix model

Following Kostov and Ben-Menahem, we calculate the two-puncture correlation function for the one-dimensional matrix model. We find that it depends on the details of discretization for all momenta p. Its only universal features are its vanishing as p → 0 and the appearance of double poles at |p| = n/√′, N = 1,2,…. We show how to derive these double poles in the conformal gauge treatment of Liouville gravity.     

Visualisation of changes in regional cerebral blood flow (rCBF) produced by ketamine using long TE gradient-echo sequences: Preliminary results

Autoradiographic studies have shown that low dose ketamine produces increases in regional glucose utilisation and blood flow in the hippocampus, cerebral cortex, and olfactory lobe in the rat brain, probably due to antagonism at the NMDA receptor. Functional MRI using deoxyhaemoglobin contrast can be used to study changes in regional cerebral blood flow (rCBF). Long TE gradient-echo sequences were used to study changes in rCBF produced by low dose ketamine in rats anaesthetised with nitrous oxide, supplemented with either halothane (HAL) or fentanyl/fluanisone/midazolam (FFM) combination. Images from rats in the FFM group showed a 10–14% increase in signal intensity in the hippocampus, cerebral cortex, and olfactory lobe following either a single bolus or a low dose infusion of ketamine (p < .05). These changes were significantly reduced in the HAL group (p < .005). Halothane is known to attenuate the changes in regional glucose utilisation produced by the noncompetitive NMDA antagonist dizocilpine (MK-801), and its effects on ketamine-induced changes in rCBF seen in this study may be due to a similar effect. The potential use of functional MRI in studying the effect of pharmacological interventions on rCBF is discussed.     

Investigation of cerebral ischemia using magnetization transfer contrast (MTC) MR imaging

The effects of cerebral ischemia in rat brain were monitored as a function of time using proton MR imaging. Spinspin relaxation time (T₂), proton density, and magnetization transfer contrast (MTC) were measured by MR imaging at various time intervals during a 1-week period following the induction of ischemic damage. Ischemic injury was characterized by a maximization of both T₂ value and MTC appearance at 24 hr postischemic injury. These changes were accompanied by a gradual increase in MR observable water density over the first few days of ischemia. A reduction in the magnetization exchange rate between “free” and “bound” water protons as measured by MTC imaging is at least partially responsible for the elevation in T₂ values observed during ischemia, and may accompany breakdown of cellular structure.     

Proton magnetic resonance spectroscopic images and MRI volumetric studies for lateralization of temporal lobe epilepsy

We obtained 2D magnetic resonance (MR) spectroscopic images (MRSI) and MRI volumetric measurements (MRIV) of amygdala and hippocampus in 30 consecutive patients with temporal lobe epilepsy (TLE) being evaluated for surgical treatment. Both MRSI and MRIV lateralization showed good agreement with the current gold standard of clinical-EEG lateralization. Each exam separately correctly lateralized 25 out of 30 patients with no false lateralization. Combining both exams, lateralization could be achieved in 28 out of 30 patients. The two patients with no significant asymmetry had bitemporal EEG abnormalities, and bilateral damage on both MRIV and MRSI. There was a good correlation between the magnitude of the MRSI and MRIV asymmetry (Pearson COEFFICIENT = 0.83; p < .0001). Both MRSI and MRIV were normal in our patients with seizures originating outside the temporal lobes. Both MRIV and MRSI can lateralize TLE in 83% of patients. Combination of the two modalities allows lateralization in 93% of patients. Patients who cannot be lateralized generally have symmetrical bitemporal abnormalities; they are not incorrectly lateralized. The structural and chemical pathologic abnormalities seen in TLE seem to be associated with the seizure focus, and may be as, or even more, reliable than a few recorded seizures in predicting the side from which most seizures originate.     

Projective and affine connections on S and integrable systems

It is known that the Korteweg–de Vries (KdV) equation is a geodesic flow of an L² metric on the Bott–Virasoro group. This can also be interpreted as a flow on the space of projective connections on S¹. The space of differential operators Δ⁽ⁿ⁾=∂ⁿ+u₂∂ⁿ⁻²++u_n form the space of extended or generalized projective connections. If a projective connection is factorizable Δ⁽ⁿ⁾=(∂−((n+1)/2−1)p₁)(∂+(n−1)/2p_n) with respect to quasi primary fields p_i’s, then these fields satisfy ∑_i=1ⁿ((n+1)/2−i)p_i=0. In this paper we discuss the factorization of projective connection in terms of affine connections. It is shown that the Burgers equation and derivative non-linear Schrödinger (DNLS) equation or the Kaup–Newell equation is the Euler–Arnold flow on the space of affine connections.     

Source abundances of ultra heavy elements derived from UHCRE measurements

A total of 205 tracks have been located, measured, and positively identified as originating from Ultra Heavy (Z ≥ 65) cosmic ray ions with energies over 2 GeV/amu in the 10 UHCRE plastic track detector (mainly Lexan polycarbonate) stacks studied by our Group. About 40 values of reduced etch rate S have been obtained along each of these tracks. A method based on determining the gradient of S, together with calibration in accelerators, is used to determine the charge of each ion resulting in one of such tracks to obtain the charge spectrum of the recorded Ultra Heavy ions. The abundance ratio of ions with 87 ≤ Z ≤ 100, to those with 74 ≤ Z ≤ 86, as well as that of ions with 81 ≤ Z ≤ 86 to those with 74 ≤ Z ≤ 80 are calculated at 0.016 and 0.32, respectively, which agree with the values obtained from measurements in the HEAO-3 and Ariel-6 experiments. The abundance ratio of ions with 70 ≤ Z ≤ 73 to those with 74 ≤ Z ≤ 86 is also calculated, but its value (0.074) did not seem to be significant because of our detectors' low registration efficiency in the charge range 70 ≤ Z ≤ 73. A computer program developed by our Group, based on the Leaky Box cosmic ray propagation model, has been used to determine the source abundances of cosmic ray nuclei with Z ≥ 65 inferred from the abundances measured in the UHCRE. It appeared that r-process synthesized elements were overabundant compared to the Solar System abundances, as predicted by other authors.