Evaluation of a multiple spin- and gradient-echo (SAGE) EPI acquisition with SENSE acceleration: Applications for perfusion imaging in and outside the brain

Perfusion-based changes in MR signal intensity can occur in response to the introduction of exogenous contrast agents and endogenous tissue properties (e.g. blood oxygenation). MR measurements aimed at capturing these changes often implement single-shot echo planar imaging (ssEPI). In recent years ssEPI readouts have been combined with parallel imaging (PI) to allow fast dynamic multi-slice imaging as well as the incorporation of multiple echoes. A multiple spin- and gradient-echo (SAGE) EPI acquisition has recently been developed to allow measurement of transverse relaxation rate (R₂ and R₂^?) changes in dynamic susceptibility contrast (DSC)-MRI experiments in the brain. With SAGE EPI, the use of PI can influence image quality, temporal resolution, and achievable echo times. The effect of PI on dynamic SAGE measurements, however, has not been evaluated. In this work, a SAGE EPI acquisition utilizing SENSE PI and partial Fourier (PF) acceleration was developed and evaluated. Voxel-wise measures of R₂ and R₂^? in healthy brain were compared using SAGE EPI and conventional non-EPI multiple echo acquisitions with varying SENSE and PF acceleration. A conservative SENSE factor of 2 with PF factor of 0.73 was found to provide accurate measures of R₂ and R₂^? in white (WM) (r_R2 = [0.55–0.79], r_R2? = [0.47–0.71]) and gray (GM) matter (r_R2 = [0.26–0.59], r_R2? = [0.39–0.74]) across subjects. The combined use of SENSE and PF allowed the first dynamic SAGE EPI measurements in muscle, with a SENSE factor of 3 and PF factor of 0.6 providing reliable relaxation rate estimates when compared to multi-echo methods. Application of the optimized SAGE protocol in DSC-MRI of high-grade glioma patients provided T₁ leakage-corrected estimates of CBV and CBF as well as mean vessel diameter (mVD) and simultaneous measures of DCE-MRI parameters K^trans and v_e. Likewise, application of SAGE in a muscle reperfusion model allowed dynamic measures of R₂′, a parameter that has been shown to correlate with muscle oxy-hemoglobin saturation.     

Mismatch between Cerebral Blood Volume and Flow Index during Transient Focal Ischemia Studied with MRI and Gd-BOPTA

We investigated the regional and temporal changes in cerebral blood volume (CBV), cerebral blood flow (CBF), and vascular transit time in seven mongrel cats during 30 min transient focal ischemia, caused by occlusion of the middle cerebral artery. Dynamic susceptibility contrast magnetic resonance imaging was done at 4.7 T, using fast gradient echo T₂¹ weighted imaging and intravenous injection of gadolinium-BOPTA/Dimeglumine. During occlusion, the areas showing a blood volume change were predominantly within the middle cerebral artery territory and could be divided into areas showing either CBV increases or decreases. The area with decreased blood volume also had decreased blood flow as measured by our flow-based index (p < 0.05) and was located in the central territory of the middle cerebral artery. Peripheral to this region was an area showing increased blood volume but without significant CBF changes (p > 0.05). During reperfusion, the CBF increased in the entire zone showing changes in blood volume during occlusion, and remained significantly elevated until 45 min post-occlusion, while CBV remained elevated in the hyperemic rim for at least 2 h. The presence of a peri-ischemic zone showing flow/volume mismatch identified a region wherein baseline CBF is maintained by means of compensatory vasodilatation, but where the ratio of CBF to CBV is decreased. Dynamic susceptibility contrast magnetic resonance imaging with gadolinium-BOPTA/Dimeglumine may be a valuable technique for the investigation of regional and temporal perturbations of hemodynamics during ischemia and reperfusion.     

Comparison of tumor histology to dynamic contrast enhanced magnetic resonance imaging-based physiological estimates

Purpose

The purpose of this study was to compare histologically determined cellularity and extracellular space to dynamic contrast-enhanced magnetic resonance imaging (DCE MRI)-based maps of a two-compartment model's parameters describing tumor contrast agent extravasation, specifically tumor extravascular extracellular space (EES) volume fraction (v_e), tumor plasma volume fraction (v_p) and volume-normalized contrast agent transfer rate between tumor plasma and interstitium (K_TRANS/V_T).

Materials and Methods

Obtained v_e, v_p and K_TRANS/V_T maps were estimated from gadolinium diethylenetriamine penta-acetic acid DCE T₁-weighted gradient-echo images at resolutions of 469, 938 and 2500 μm. These parameter maps were compared at each resolution to histologically determined tumor type, and the high-resolution 469-μm maps were compared with automated cell counting using Otsu's method and a color-thresholding method for estimated intracellular (V_{intracellular}) and extracellular (V_{extracellular}) space fractions.

Results

The top five K_TRANS/V_T values obtained from each tumor at 469 and 938 μm resolutions are significantly different from those obtained at 2500 μm (P<.0001) and from one another (P=.0014). Using these top five K_TRANS/V_T values and the corresponding tumor EES volume fractions v_e, we can statistically differentiate invasive ductal carcinomas from noninvasive papillary carcinomas for the 469- and 938-μm resolutions (P=.0017 and P=.0047, respectively), but not for the 2500-μm resolution (P=.9008). The color-thresholding method demonstrated that v_e measured by DCE MRI is statistically similar to histologically determined EES. The V_{extracellular} obtained from the color-thresholding method was statistically similar to the v_e measured with DCE MRI for the top 10 K_TRANS/V_T values (P>.05). DCE MRI-based K_TRANS/V_T estimates are not statistically correlated with histologically determined cellularity.

Conclusion

DCE MRI estimates of tumor physiology are a limited representation of tumor histological features. Extracellular spaces measured by both DCE MRI and microscopic analysis are statistically similar. Tumor typing by DCE MRI is spatial resolution dependent, as lower resolutions average out contributions to voxel-based estimates of K_TRANS/V_T. Thus, an appropriate resolution window is essential for DCE MRI tumor diagnosis. Within this resolution window, the top K_TRANS/V_T values with corresponding v_e are diagnostic for the tumor types analyzed in this study.     

Prediction of survival and progression in glioblastoma patients using temporal perfusion changes during radiochemotherapy

BackgroundThe aim of this study was to investigate changes in structural magnetic resonance imaging (MRI) according to the RANO criteria and perfusion- and permeability related metrics derived from dynamic contrast-enhanced MRI (DCE) and dynamic susceptibility contrast MRI (DSC) during radiochemotherapy for prediction of progression and survival in glioblastoma.MethodsTwenty-three glioblastoma patients underwent biweekly structural and perfusion MRI before, during, and two weeks after a six weeks course of radiochemotherapy. Temporal trends of tumor volume and the perfusion-derived parameters cerebral blood volume (CBV) and blood flow (CBF) from DSC and DCE, in addition to contrast agent capillary transfer constant (K^trans) from DCE, were assessed. The patients were separated in two groups by median survival and differences between the two groups explored. Clinical- and MRI metrics were investigated using univariate and multivariate survival analysis and a predictive survival index was generated.ResultsMedian survival was 19.2 months. A significant decrease in contrast-enhancing tumor size and CBV and CBF in both DCE- and DSC-derived parameters was seen during and two weeks past radiochemotherapy (p < 0.05). A 10%/30% increase in K^trans/CBF two weeks after finishing radiochemotherapy resulted in significant shorter survival (13.9/16.8 vs. 31.5/33.1 months; p < 0.05). Multivariate analysis revealed an index using change in K^trans and relative CBV from DSC significantly corresponding with survival time in months (r² = 0.843; p < 0.001).ConclusionsSignificant temporal changes are evident during radiochemotherapy in tumor size (after two weeks) and perfusion-weighted MRI-derived parameters (after four weeks) in glioblastoma patients. While DCE-based metrics showed most promise for early survival prediction, a multiparametric combination of both DCE- and DSC-derived metrics gave additional information.     

A comprehensive evaluation and impact of normalization of generalized tracer kinetic model parameters to characterize blood-brain-barrier permeability in normal-appearing and tumor tissue regions of patients with glioma

Rationale and objectivesTo comprehensively evaluate robustness and variations of DCE-MRI derived generalized-tracer-kinetic-model (GTKM) parameters in healthy and tumor tissues and impact of normalization in mitigating these variations on application to glioma.Materials (patients) and methodsA retrospective study included pre-operative 31 high-grade-glioma(HGG), 22 low-grade-glioma(LGG) and 33 follow-up data from 10 patients a prospective study with 4 HGG subjects. Voxel-wise GTKM was fitted to DCE-MRI data to estimate K^trans, v_e, v_b. Simulations were used to evaluate noise sensitivity. Variation of parameters with-respect-to arterial-input-function (AIF) variation and data length were studied. Normalization of parameters with-respect-to mean values in gray-matter (GM) and white-matter (WM) regions (GM-Type-2, WM-Type-2) and mean curves (GM-Type-1, WM-Type-1) were also evaluated. Co-efficient-of-variation(CoV), relative-percentage-error (RPE), Box-Whisker plots, bar graphs and t-test were used for comparison.ResultsGTKM was fitted well in all tissue regions. K^trans and v_e in contrast-enhancing (CE) has shown improved noise sensitivity in longer data. v_b was reliable in all tissues. Mean AIF and C(t) peaks showed ~38% and ~35% variations. During simulation, normalizations have mitigated variations due to changes in AIF amplitude in K^trans and v_b.. v_e was less sensitive to normalizations. CoV of K^trans and v_b has reduced ~70% after GM-Type-1 normalization and ~80% after GM-Type-2 normalization, respectively. GM-Type-1 (p = 0.003) and GM-Type-2 (p = 0.006) normalizations have significantly improved differentiation of HGG and LGG using K^trans.ConclusionK^trans and v_b can be reliably estimated in normal-appearing brain tissues and can be used for normalization of corresponding parameters in tumor tissues for mitigating inter-subject variability due to errors in AIF. Normalized K^trans and v_b provided improved differentiation of HGG and LGG.     

Can transverse relaxation rates in deep gray matter be approximated from functional and T2-weighted FLAIR scans for relative brain iron quantification?

Alterations in iron concentration in certain deep gray matter regions are known to occur in aging and several clinical conditions. In vivo measurements of R₂¹ transverse relaxation rates and quantitative susceptibility mapping (QSM) have been shown to be strongly correlated with iron concentration in tissue, but their calculation requires the acquisition of a multi-echo gradient recalled echo sequence (MGRE). In the current study, we examined the feasibility of approximating R₂¹ rates using metrics derived from fMRI-EPI and T₂-weighted FLAIR images, which are widely available. In a sample of 40 healthy subjects, we obtained these metrics (v_EPI and v_FLAIR), as well as R₂¹ rates and QSM estimates, and found significant correlations between v_EPI and v_FLAIR and R₂¹ rates in several subcortical gray matter regions known to accumulate iron, but not in a control corticospinal white matter region. These relationships were preserved after referencing v_EPI and v_FLAIR with respect to the values in the control region. Effect sizes (above 0.5 for some of the regions, particularly the largest ones) were calculated and put in relation to those of the correlation between QSM and R₂¹ rates. We propose that the metrics described here may be applied, possibly in a retrospective fashion, to analyze datasets with available EPI or T₂-weighted FLAIR scans (and lacking a MGRE sequence), to devise new hypotheses regarding links between iron concentration in brain tissue and other variables of interest.     

Quantification of cerebral perfusion using the "bookend technique": an evaluation in CNS tumors

We present a method of quantifying cerebral blood volume using dynamic susceptibility contrast. Our approach combines T₂-weighted echo planar imaging (EPI) pulse sequences and reference scans that determine the parenchymal T₁ changes resulting from an injection of a gadolinium chelate. This combined T₂- and T₁-weighted approach (the “bookend” technique) has been shown to be effective in the quantification of gradient-echo (GRE) (T₂*-weighted) perfusion images but has not been applied to spin-echo EPI (SE-EPI) (T₂-weighted) images. The physics related to blood volume measurement based on T₂- and T₂*-weighted EPI sequences is known to be different, and there is a question as to whether the bookend approach is effective with SE-EPI. We have compared the quantitative SE-EPI with GRE-EPI in a series of patients with central nervous system (CNS) tumors. We found that quantitative cerebral blood volume (qCBV) values for SE-EPI and GRE-EPI are in agreement with each other and with historical reference values. A subjective evaluation of image quality showed that image quality in the SE-EPI scans was high and exhibited high interreader agreement. We conclude that measuring qCBV using the bookend technique with SE-EPI images is possible and may be a viable alternative to GRE-EPI in the evaluation of CNS tumors.     

Complementary use of T2-weighted and postcontrast T1- and T21-weighted imaging to distinguish sites of reversible and irreversible brain damage in focal ischemic lesions in the rat brain

The evolution of a photochemically induced cortical infarct was monitored using T₂-, postcontrast (GdDOTA) T₁-, and postcontrast (DyDTPA-BMA) T₂¹-weighted NMR imaging techniques. Data acquired with these different NMR imaging types were compared, both qualitatively and quantitatively. The T₂¹-weighted NMR images after sprodiamide injection (DyDTPA-BMA) were perfusion-weighted images that allowed the differentiation between several infarct-related areas in terms of different degrees of perfusion deficiency. No quantitative information on cerebral blood flow (CBF) was obtained. A clear distinction was made between areas with a complete lack of CBF located in the core of the lesion and temporary CBF insufficiencies in the rim surrounding this core. Concomitant observations on T₂-weighted and postcontrast T₁-weighted images revealed the same temporary rim characterized by an increased water content, and an intact blood-brain barrier (BBB), as well as by reduced perfusion. This rim appeared within the first hours after infarct induction, reached a maximum 24 h later, and lasted between 3–5 days, when its size gradually decreased until complete disappearance. These observations suggest the existence of an area at risk. Only on postcontrast T₁-weighted images, the core of the lesion remained visible during the whole experimental period (10 days) and reflected in all likelihood the irreversibly damaged ischemic central core. The combined application of different NMR imaging techniques when studying focal cerebral infarctions in the rat brain allowed us to distinguish, in terms of NMR characteristics, zones of reversible from irreversible brain damage and to estimate the severity of the damage. This might offer an appropriate experimental setup for the screening of cerebroprotective compounds.     

Magnetic,optical and relaxometric properties of organically coated gold–magnetite (Au–Fe3O4) hybrid nanoparticles for potential use in biomedical applications

We present the magnetic, optical and relaxometric properties of multifunctional Au–Fe₃O₄ hybrid nanoparticles (HNPs), as possible novel contrast agents (CAs) for magnetic resonance imaging (MRI). The HNPs have been synthesized by wet chemical methods in heterodimer and core–shell geometries and capped with oleylamine. Structural characterization of the samples have been made by X-ray diffraction and transmission electron microscopy, while magnetic properties have been investigated by means of Superconducting Quantum Interference Device-SQUID magnetometry experiments. As required for MRI applications using negative CAs, the samples resulted superparamagnetic at room temperature and well above their blocking temperatures. Optical properties have been investigated by analyzing the optical absorbtion spectra collected in UV–visible region. Relaxometric measurements have been performed on organic suspensions of HNPs and Nuclear Magnetic Resonance (NMR) dispersion curves have been obtained by measuring the longitudinal 1/T₁ and transverse 1/T₂ relaxation rates of solvent protons in the range 10 kHz/300 MHz at room temperature. NMR relaxivities r₁ and r₂ have been compared with ENDOREM^®, one of the commercial superparamagnetic iron oxide based MRI contrast agents. MRI contrast enhancement efficiencies have been investigated also by examining T₂-weighted MR images of suspensions. The experimental results suggest that the nanoparticles' suspensions are good candidates as negative CAs.     

Electronic states of the c is - and trans - H3ONO molecules: a CASPT2 study

The CASPT2 calculations for the S₀, T₁, S₁, T₂, and S₂ states of the cis- and trans-CH₃ONO molecules predict the energy levels and geometries of the cis- and trans-isomers in the different states. The CASPT2 adiabatic (T ₀) and vertical (T _v) excitation energies are in good agreement with available experimental data (for the S₁ cis- and trans-isomers). The CH₃O-NO dissociation potential energy curves were calculated at the CASPT2//CASSCF level, and the CASPT2 calculations were performed for the transition states along the T₁, S₁, and T₂ dissociation paths. For the repulsive S₂ state the calculations predict the T _v values larger than 5.4 eV and dissociation products of CH₃O (1²A″) + NO (X²Π).     

Measurement of hydrogen- and self-broadened half-widths of ammonia at 200 and 300°K

The hydrogen- and self-broadened half-widths have been measured for the (v₁+v₂)- and (v₂+v₃)-bands of ammonia at 300 and 207°K. Measurement of hydrogen-broadened widths has been restricted to J, K ?6, but that of self-broadened widths is done for a few lines outside that range. Assuming a power-law dependence of half-width on temperature given by γ(T)=γ(T₀)(T/T₀)^α, the average value of the index α for the lines measured is found to be 0·57 for hydrogen broadening.     

MRI phantom for tissue simulation with respect to diffusion coefficient and kurtosis - Validation with injection of liposomal theranostics

This study presents gelatine-based and agar-based phantoms with an addition of glycerol, safflower oil, silicone oil and cellulose microcrystalline with a potential to cover the entire range of tissue diffusion coefficients and kurtosis values. Forty types of phantoms were prepared and examined for NMR relaxation times T₁ and T₂ and diffusional metrics D, K and ADC. Wide ranges of values of D (0.0003–0.0031 mm²s⁻¹), K (0.00–7.24) and ADC (0.0002–0.0031 mm²s⁻¹) were observed. Two of the phantoms closely mimic muscle and cortical gray matter with respect to water diffusion parameters. Although many of the presented phantoms display both D and K values within the range of human tissues, they match different tissues with respect to D and K. The imaging results for the gray matter simulating phantom injected with the liposomal solution, bear a resemblance to the particle size effect described in the literature. The phantoms presented in this work are simple in preparation and affordable tissue-simulating materials to be used primarily in development of diffusion kurtosis-based MRI methods and possibly in a preliminary assessment of MRI contrast agents. Further adjustments of the chemical compositions could potentially lead to development of new types of phantoms mimicking diffusional properties of more kinds of soft tissues.     

Geometric study of the connection between the Lagrangian and Hamiltonian constraints

The second order differential equation character of the solutions of the dynamical equation i(Γ)ω_L = dE_L for a singular Lagrangian L, as well as the conditions for the existence of such a solution, are studied. We also introduce a couple of maps R (L)_v : T _FL(v)(T¹Q) → T_v(TQ) and T(L)_v : T_FL(v)(T¹Q) → T_FL(v)(T¹Q), with v ϵ TQ, which are shown to be very useful for establishing the connection between the constraints arising in the Lagrangian and Hamiltonian formulations.     

Dynamic contrast-enhanced magnetic resonance imaging parameters independent of baseline T10 values

A baseline T₁₀ value is typically needed for dynamic contrast-enhanced (DCE-) MRI studies. However, an assumed baseline T₁₀ has to be used when T₁₀ measurements for patients are not available. In this work, we systematically investigate the dependence on T₁₀ of the commonly used DCE-MRI parameters (K^trans, k_ep, v_e and IAUC) as well as several newly defined parameters [the normalized ratios (NRs) of k_ep, K^trans and v_e, which are measures of relative changes in these parameters between two time points] for a spoiled gradient-echo pulse sequence using simulations and in vivo studies. Effects of various factors on the T₁₀ dependence, such as the true T₁₀ value, flip angle and the potential changes in T₁₀ due to treatment, were also assessed using simulations. We found that DCE-MRI parameters k_ep and the NR of k_ep are largely independent of T₁₀, especially when larger flip angles are used (e.g., 30–40°). Their estimations therefore do not require any knowledge of T₁₀. The NRs of K^trans, v_e and IAUC also exhibit independence to T₁₀, but only when T₁₀ remains constant between pre- and posttreatment. The estimation of parameters themselves (K^trans, v_e and IAUC) is highly dependent on the T₁₀ value.     

In Vivo Relaxation Time Measurements in the Human Placenta Using Echo Planar Imaging at 0.5 T

This paper presents the first in vivo measurements of the nuclear magnetic resonance relaxation times T₁ and T₂ at 0.5 T in the human placenta from 20 weeks gestational age until term, in both normal and compromised pregnancies. T₁ measurements were performed by using both an inversion recovery sequence and the Look-Locher echo planar imaging (EPI) sequence on a total of 41 women with normal pregnancies and 11 women with compromised pregnancies. T₂ measurements were performed by using a spin-echo EPI sequence on 36 women with normal pregnancies and 14 women with compromised pregnancies. In normal pregnancies, both the T₁ values measured with the inversion recovery sequence and the T₂ values were found to decrease with gestational age, the linear regression results gave T₁=−9.1t+1538 r²=0.23 p=0.03 T₂=−4.0t+338 r²=0.47 p=4 10⁻⁶ where t is the gestational age in weeks, and T₁ and T₂ are the relaxation times in milliseconds. T₁ values measured very rapidly with the Look-Locher EPI sequence, but, therefore, with a much lower signal-to-noise ratio, showed no significant trends.The T₁ values measured in the abnormal group were significantly lower than those measured in the normal group. Four out of eight patients with compromised pregnancies had placental T₁ values lying outside the 90% confidence limits for the normal population based about the regression line, significantly more than expected by chance (p = 0.005). Ten out of fourteen of the T₂ measurements in the abnormal group were below the regression line established for the normal group, with 4 lying below the 90% confidence interval, although these trends were only just significant (p = 0.06 and p = 0.03).     

Infrared absorption intensities of nitrous acid (HONO) fundamental bands

A Fourier transform spectrometer with a resolution of 0.06 cm^-1 was used to measure the absorption intensities of the four in-plane fundamental bands (v₁, v₂, v₃ and v₄) of trans-nitrous acid (HONO) and three of the in-plane fundamental bands (v₁, v₂ and v₄) of cis-nitrous acid. The equilibrium constants for the reactions NO + NO₂ + H₂O?2HONO, NO + NO₂?N₂O, and 2NO₂?N₂O₄ were used to determine the partial pressure of HONO in the gas mixture in the absorption cell. Interferences from overlapping absorptions of NO₂, H₂O and other species were digitally subtracted from the spectra.     

Bi-Exponential T2 Decay in Dairy Cream Phantoms

MRI phantoms are an important part of any experiment because they provide a reference of known parameters. There are many choices of mono-exponential T₂ phantoms, but few choices for bi-exponential T₂ phantoms. We have found that dairy cream provides an excellent bi-exponential T₂ model with similar relaxation times to those found in white matter. Five cream phantoms of different milk fat percentages (2, 6, 10, 18 and 35%) were imaged with an optimized Carr–Purcell–Meiboom–Gill sequence. The decay curves for each of the phantoms were fit using Non-Negative Least Squares. We found that the short T₂ component fraction relative to the total energy in the distribution correlated linearly (r = 0.9973) with the milk fat percentage. The short T₂ time was 38 ± 4 ms and the long T₂ time was 135 ± 4 ms.     

Charged hyperpions,charged higgs bosons and the leptonic decays of the heavy open-top mesonsT b * andT b

We study the leptonic decay modes of the vectorT _b ^* and pseudoscalarT _b t-flavored mesons in the framework of some extended technicolor models and for the standardSU(2)×U(1) model with two complex Higgs doublets. We find that the ratioГ(T _b ^* →? v Г(T →? v) bcan help in discriminating among these models but, unfortunately, the experimental prospects for detecting these decay modes are not very bright.     

Quadrupole interaction of117In in Zn metal

We have used the TDPAC method to measure the temperature dependence of the quadrupole interaction frequencyv _Q of¹¹⁷In in Zn lattice. The observedv _Q reduces from 187.4 (20) MHz at 77°K to 155.3 (20) MHz at 673°K. The variation ofv _Q is seen to be proportional toT ^3/2.