In the context of neurologic disorders, dynamic susceptibility contrast (DSC) and dynamic contrast enhanced (DCE) MRI provide valuable insights into cerebral vascular function, integrity, and architecture. Even after two decades of use, these modalities continue to evolve as their biophysical and kinetic basis is better understood, with improvements in pulse sequences and accelerated imaging techniques and through application of more robust and automated data analysis strategies. Here, we systematically review each of these elements, with a focus on how their integration improves kinetic parameter accuracy and the development of new hemodynamic biomarkers that provide sub-voxel sensitivity (e.g., capillary transit time and flow heterogeneity). Regarding contrast mechanisms, we discuss the dipole-dipole interactions and susceptibility effects that give rise to simultaneous T, T and T relaxation effects, including their quantification, influence on pulse sequence parameter optimization, and use in methods such as vessel size and vessel architectural imaging. The application of technologic advancements, such as parallel imaging, simultaneous multi-slice, undersampled k-space acquisitions, and sliding window strategies, enables improved spatial and/or temporal resolution of DSC and DCE acquisitions. Such acceleration techniques have also enabled the implementation of, clinically feasible, simultaneous multi-echo spin- and gradient echo acquisitions, providing more comprehensive and quantitative interrogation of T, T and T changes. Characterizing these relaxation rate changes through different post-processing options allows for the quantification of hemodynamics and vascular permeability. The application of different biophysical models provides insight into traditional hemodynamic parameters (e.g., cerebral blood volume) and more advanced parameters (e.g., capillary transit time heterogeneity). We provide insight into the appropriate selection of biophysical models and the necessary post-processing steps to ensure reliable measurements while minimizing potential sources of error. We show representative examples of advanced DSC- and DCE-MRI methods applied to pathologic conditions affecting the cerebral microcirculation, including brain tumors, stroke, aging, and multiple sclerosis. The maturation and standardization of conventional DSC- and DCE-MRI techniques has enabled their increased integration into clinical practice and use in clinical trials, which has, in turn, spurred renewed interest in their technological and biophysical development, paving the way towards a more comprehensive assessment of cerebral hemodynamics.

Magnetic resonance imaging (MRI) based diffusion tensor imaging (DTI) can assess white matter (WM) integrity through several metrics, such as fractional anisotropy (FA), axial/radial diffusivities (AxD/RD), and mode of anisotropy (MA). Standard DTI is susceptible to the effects of extracellular free water (FW), which can be removed using an advanced free-water DTI (FW-DTI) model. The purpose of this study was to compare standard and FW-DTI metrics in the context of Alzheimer’s disease (AD). Data were obtained from the Open Access Series of Imaging Studies (OASIS-3) database and included both healthy controls (HC) and mild-to-moderate AD. With both standard and FW-DTI, decreased FA was found in AD, mainly in the corpus callosum and fornix, consistent with neurodegenerative mechanisms. Widespread higher AxD and RD were observed with standard DTI; however, the FW index, indicative of AD-associated neurodegeneration, was significantly elevated in these regions in AD, highlighting the potential impact of free water contributions on standard DTI in neurodegenerative pathologies. Using FW-DTI, improved consistency was observed in FA, AxD, and RD, and the complementary FW index was higher in the AD group as expected. With both standard and FW-DTI, higher values of MA coupled with higher values of FA in AD were found in the anterior thalamic radiation and cortico-spinal tract, most likely arising from a loss of crossing fibers. In conclusion, FW-DTI better reflects the underlying pathology of AD and improves the accuracy of DTI metrics related to WM integrity in Alzheimer’s disease.

A recent quantum computing paper ͑G. S. Uhrig, Phys. Rev. Lett. 98, 100504 ͑2007͒͒ analytically derived optimal pulse spacings for a multiple spin echo sequence designed to remove decoherence in a two-level system coupled to a bath. The spacings in what has been called a "Uhrig dynamic decoupling ͑UDD͒ sequence" differ dramatically from the conventional, equal pulse spacing of a Carr-Purcell-Meiboom-Gill ͑CPMG͒ multiple spin echo sequence. The UDD sequence was derived for a model that is unrelated to magnetic resonance, but was recently shown theoretically to be more general. Here we show that the UDD sequence has theoretical advantages for magnetic resonance imaging of structured materials such as tissue, where diffusion in compartmentalized and microstructured environments leads to fluctuating fields on a range of different time scales. We also show experimentally, both in excised tissue and in a live mouse tumor model, that optimal UDD sequences produce different T 2 -weighted contrast than do CPMG sequences with the same number of pulses and total delay, with substantial enhancements in most regions. This permits improved characterization of low-frequency spectral density functions in a wide range of applications.

Purpose A simplified acquisition and analysis approach for spin- and gradient-echo (SAGE) based DSC-MRI data that is free of contrast agent T1 leakage effects is proposed. Methods A five-echo SAGE sequence was used to acquire DSC-MRI data in rat C6 tumors (n=7). Non-linear fitting of all echoes was performed to obtain T1-insensitive ΔR2* and ΔR2 time series. The simplified approach, which includes two gradient echoes and one spin echo, was also used to analytically compute T1-insensitive ΔR2*, using the two gradient echoes, and ΔR2, using all three echoes. The blood flow, blood volume and vessel size values derived from each method were compared. Results In all cases, the five-echo and simplified SAGE ΔR2* and ΔR2 were in excellent agreement and demonstrated significant T1-leakage correction compared to the uncorrected single-echo data. The derived hemodynamic parameters for blood volume, blood flow and vessel size were not significantly different between the two methods. Conclusions The proposed simplified SAGE technique enables the acquisition of gradient and spin echo DSC-MRI data corrected for T1 leakage effects, yields parameters that are in agreement with the five echo SAGE, and does not require non-linear fitting to extract ΔR2* and ΔR2 time series.

Background and Purpose: The accuracy of DSC-MRI CBV maps in glioblastoma depends on acquisition and analysis protocols. Multi-site protocol heterogeneity has challenged standardization initiatives due to the difficulties of in vivo validation. This study seeks to compare the accuracy of routinely used protocols using a digital reference object (DRO). Methods: The DRO consists of approximately 10,000 simulated voxels recapitulating typical signal heterogeneity encountered in vivo. The influence of acquisition and post-processing methods on CBV reliability was evaluated across 6,912 parameter combinations, including contrast agent dosing schemes, pulse sequence parameters, field strengths, and post-processing methods. Accuracy and precision were assessed using the concordance correlation coefficient (CCC) and coefficient of variation (CV). Results: Across all parameter space, the optimal protocol includes full-dose contrast agent preload and bolus, intermediate (60°) flip angle, 30 ms TE, and post-processing with a leakage correction algorithm (CCC = 0.97, CV = 6.6%). Protocols with no preload or fractional-dose preload and bolus using these acquisition parameters were generally less robust. However, a protocol with no preload, full-dose bolus, and low (30°) flip angle performed very well (CCC = 0.93, CV = 8.7% at 1.5T) and (CCC = 0.92, CV = 8.2% at 3T). Conclusion: Schemes with full-dose preload and bolus maximize CBV accuracy and reduce variability, which could enable smaller sample sizes and more reliable detection of CBV changes in clinical trials. When lower total contrast agent dose is desired, use of a low flip angle, no preload, full-dose bolus protocol may provide an attractive alternative.