Evaluation of pressure‐driven brain infusions in nonhuman primates by intra‐operative 7 tesla MRI

Purpose:

To characterize the effects of pressure‐driven brain infusions using high field intra‐operative MRI. Understanding these effects is critical for upcoming neurodegeneration and oncology trials using convection‐enhanced delivery (CED) to achieve large drug distributions with minimal off‐target exposure.

Materials and Methods:

High‐resolution T2‐weighted and diffusion‐tensor images were acquired serially on a 7 Tesla MRI scanner during six CED infusions in nonhuman primates. The images were used to evaluate the size, distribution, diffusivity, and temporal dynamics of the infusions.

Results:

The infusion distribution had high contrast in the T2‐weighted images. Diffusion tensor images showed the infusion increased diffusivity, reduced tortuosity, and reduced anisotropy. These results suggested CED caused an increase in the extracellular space.

Conclusion:

High‐field intra‐operative MRI can be used to monitor the distribution of infusate and changes in the geometry of the brain's porous matrix. These techniques could be used to optimize the effectiveness of pressure‐driven drug delivery to the brain. J. Magn. Reson. Imaging 2012; 36:1339–1346. © 2012 Wiley Periodicals, Inc.     

NMR‐based diffusion pore imaging by double wave vector measurements

One main interest of nuclear magnetic resonance (NMR) diffusion experiments is the investigation of boundaries such as cell membranes hindering the diffusion process. NMR diffusion measurements allow collecting the signal from the whole sample. This mainly eliminates the problem of vanishing signal at increasing resolution. It has been a longstanding question if, in principle, the exact shape of closed pores can be determined by NMR diffusion measurements. In this work, we present a method using short diffusion gradient pulses only, which is able to reveal the shape of arbitrary closed pores without relying on a priori knowledge. In comparison to former approaches, the method has reduced demands on relaxation times due to faster convergence to the diffusion long‐time limit and allows for a more flexible NMR sequence design, because, e.g., stimulated echoes can be used. Magn Reson Med 70:836–841, 2013. © 2012 Wiley Periodicals, Inc.     

Therapy monitoring of skeletal metastases with whole‐body diffusion MRI

Current methods of assessing tumor response at skeletal sites with metastatic disease use a combination of imaging tests, serum and urine biochemical markers, and symptoms assessment. These methods do not always enable the positive assessment of therapeutic benefit to be made but instead provide an evaluation of progression, which then guides therapy decisions in the clinic. Functional imaging techniques such as whole‐body diffusion magnetic resonance imaging (MRI) when combined with anatomic imaging and other emerging “wet” biomarkers can improve the classification of therapy response in patients with metastatic bone disease. A range of imaging findings can be seen in the clinic depending on the type of therapy and duration of treatment. Successful response to systemic therapy is usually depicted by reductions in signal intensity accompanied by apparent diffusion coefficient (ADC) increases. Rarer patterns of successful treatment include no changes in signal intensity accompanying increases in ADC values (T2 shine‐through pattern) or reductions in signal intensity without ADC value changes. Progressive disease results in increases in extent/intensity of disease on high b‐value images with variable ADC changes. Diffusion MRI therapy response criteria need to be developed and tested in prospective studies in order to address current, unmet clinical and pharmaceutical needs for reliable measures of tumor response in metastatic bone disease. J. Magn. Reson. Imaging 2014;39:1049–1078 . © 2014 Wiley Periodicals, Inc .     

Partial Fourier transform reconstruction for single‐shot MRI with linear frequency‐swept excitation

A novel image encoding approach based on linear frequency‐swept excitation has been recently proposed to overcome artifacts induced by various field perturbations in single‐shot echo planar imaging. In this article, we develop a new super‐resolved reconstruction method for it using the concepts of local k‐space and partial Fourier transform. This method is superior to the originally developed conjugate gradient algorithm in convenience, image quality, and stability of solution. Reduced field‐of‐view is applied to the phase encoding direction to further enhance the spatial resolution and field perturbation immunity of the image obtained. Effectiveness of this new combined reconstruction method is demonstrated with a series of experiments on biological samples. Two single‐shot sequences with different encoding features are tested. The results show that this reconstruction method maintains excellent field perturbation immunity and improves fidelity of the images. In vivo experiments on rat indicate that this solution is favorable for ultrafast imaging applications in which severe susceptibility heterogeneities around the tissue–air or tissue–bone interfaces, motion and oblique plane effects usually compromise the echo planar imaging image quality. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Age‐related non‐Gaussian diffusion patterns in the prefrontal brain

Purpose

To characterize age‐related MR diffusion patterns of the prefrontal brain cortex microstructure using a new method for investigating the non‐Gaussian behavior of water diffusion called diffusional kurtosis imaging (DKI).

Materials and Methods

Measures of mean diffusivity (MD), fractional anisotropy (FA) and mean kurtosis (MK) were compared in the prefrontal brain cortex of 24 healthy volunteers (adolescents, young adults, and elderly) ranging from age 13 to 85 years. A Mann‐Whitney test was used to compare subject groups with respect to the diffusion measures, and linear regression was used to characterize the change in each diffusion measure as a function of age.

Results

We found significant age‐related changes in the elderly adult group, with increase of MD and decrease of FA.

Conclusion

The current study demonstrates distinct mean kurtosis patterns for different age‐ranges, with significant age‐related correlation for mean kurtosis (MK) and MK peak position, showing that diffusional kurtosis is able to characterize and measure age‐related diffusion changes for both grey and white matter, in the developing and aging brain. J. Magn. Reson. Imaging 2008;28:1345–1350. © 2008 Wiley‐Liss, Inc.