Purpose:To investigate the possibility of using combined blood oxygen level-dependent (BOLD) imaging and diffusion-weighted imaging (DWI) to detect pathological and physiological changes in renal tissue damage of the kidney induced by chronic renal hyperfiltration. Materials and Methods:The apparent diffusion coefficient (ADC) and the T 2 * value within the inner compartments of the kidneys of 17 rats with diabetes mellitus were compared with the results obtained from a control group (N ϭ 16). The influence of dynamic changes of the renal function on the blood-oxygen saturation was evaluated by comparing the T 2 * values before and after the active reduction of tubular transport by furosemide injection.Results: All compartments of the diabetic kidney showed significantly (P Ͻ 0.05) lower T 2 *-values compared to the control group. In particular, the very low values in the outer stripe (OS) of the outer medulla (OM) (T 2 *-normal: 69.4 Ϯ 10.9 msec; T 2 *-diabetic: 51.4 Ϯ 13.9 msec) indicated either hypoxia due to hyperfiltration, or renal blood volume changes. Diffusion imaging of the same area showed significantly lower ADC values (ADC-normal: 1.45 Ϯ 0.26; ADCedema: 1.19 Ϯ 0.25 [10 -9 m 2 /s]) that correlated with pathological findings on histopathology. The injection of furosemide significantly (P Ͻ 0.05) increased T 2 * in all compartments of both populations while the ADC remained unchanged.Conclusion: BOLD-contrast imaging appears to be able to depict tissue at risk from ischemia by revealing information about the balance between tubular workload and delivery of oxygen, and thus may reflect a measure of the reserve capacity. The diffusion measurements apparently reveal complementary information. Although ADC imaging is not sensitive to the current energy metabolism, it appears toreflect the pathological changes within the tissue. Therefore, ADC measurements may be a sensitive indicator of the severity of ischemic lesions.

This study characterizes the diffusion anisotropy of the human kidney using a diffusion-weighted, single-shot echo planar imaging (EPI) sequence in order to access the full apparent diffusion tensor (ADT) within one breathhold. The fractional anisotropy (FA) of the cortex and the medulla were found to be 0.22 ؎ 0.12 and 0.39 ؎ 0.11, respectively (N ‫؍‬ 10), which emphasizes the need for rotationally invariant diffusion measurements for clinical applications. Additional limitations for clinical diffusion imaging on the kidney are the strong susceptibility variations within the abdomen that restrict the use of imaging techniques employing long echo trains, and the severe motion sensitivity that limits the available imaging time to one breath-hold. To overcome these problems an isotropic, diffusion-weighted, segmented EPI protocol that facilitates the acquisition of high-resolution diffusion-weighted images within a single breath-hold was implemented. Using this method, the apparent diffusion coefficient (ADC) of the cortex and medulla were found to be 2. 89 Index terms: diffusion; magnetic resonance imaging; kidney; EPI; fractional anisotropy WATER TRANSPORT is the predominant phenomenon throughout the kidney due to the kidney's major role in water reabsorption and concentration-dilution functions. These movements are mainly located in the tubular cells and are controlled either by active or passive mechanisms, depending on their location in the nephrons. Consequently, the measurement of the diffusion characteristics of the kidney may provide useful insights into the mechanisms of various renal diseases, including chronic renal failure, renal artery stenosis, and uretral obstruction. However, renal diffusion imaging is very challenging due to the extreme motion sensitivity of diffusion-weighted sequences, and the clinical use of this technique has been hampered by both the severe motion artifacts caused by arterial pulsations and respiratory motion. Diffusion-weighted single-shot-EPI (DW-SSEPI) (1), in conjunction with single breath-hold imaging (2-6) and peripheral pulse unit (PPU) triggering, (7) has been suggested as a possible means of overcoming these problems. However, the restriction of the diffusion experiment to a single breathhold limits the possible spatial resolution and the precision of the diffusion measurement (the number of directions for the diffusion weighting, the number of b-values, and the number of averages). As a result, most studies in the literature have measured the ADC in only one direction (2,4 -7), and hence have implicitly assumed that the diffusion characteristics of the kidney are isotropic. Hydration has been shown to increase global ADC values (3), while renal artery stenosis or ureteral obstruction decreased the values (2,3). In cases of acute or chronic renal failure, the cortical and medullary ADC values were significantly lower than in normal kidneys, and the cortical values were highly correlated with the serum creatinine levels (2).Although some studies have implied that t...

Diffusion weighting improved the sensitivity of imaging in cervical spondylotic myelopathy.

The use of proton resonance frequency shift-based magnetic resonance (MR) thermometry for interventional guidance on abdominal organs is hampered by the constant displacement of the target due to the respiratory cycle and the associated thermometry artifacts. Ideally, a suitable MR thermometry method should for this role achieve a subsecond temporal resolution while maintaining a precision comparable to those achieved on static organs while not introducing significant processing latencies. Here, a computationally effective processing pipeline for two-dimensional image registration coupled with a multibaseline phase correction is proposed in conjunction with high-frame-rate MRI as a possible solution. The proposed MR thermometry method was evaluated for 5 min at a frame rate of 10 images/sec in the liver and the kidney of 11 healthy volunteers and achieved a precision of less than 2°C in 70% of the pixels while delivering temperature and thermal dose maps on the fly. The ability to perform MR thermometry and dosimetry in vivo during a real intervention was demonstrated on a porcine kidney during a high-intensity focused ultrasound heating experiment. Magn Reson Med 63:1080-1087, 2010. V C 2010 Wiley-Liss, Inc. Key words: MRI; thermometry; temperature; interventional; imaging; real time system; motion artifacts; proton resonance frequency shift; PRF MR thermometry relying on the water proton resonance frequency is gaining importance for monitoring and guiding thermal therapies such as radiofrequency (1), laser (2), or focused ultrasound thermal ablation (3-5). Typically, proton resonance frequency-based MR thermometry relies on the voxelwise evaluation of phase differences between sequentially acquired gradient echo images. However, for the use on abdominal organs, this renders the method very sensitive to motion artifacts and magnetic field changes. These motion artifacts can be coarsely classed into the two following types: intrascan motion artifacts and interscan motion artifacts. Intrascan motion artifacts are caused by displacement during the MR acquisition process and lead to image blurring and object ghosting. Commonly, this type of artifact is addressed using fast MR acquisition schemes or alternatively with respiratory-gated sequences that reduce the temporal resolution to the respiratory frequency. Interscan motion artifacts are due to organ displacement between the MR acquisitions and lead to a misregistration between subsequent phase images and thus to artifacts in the subtraction process. Furthermore, since any displacement or plastic deformation of the abdominal organs will in general also lead to a modified demagnetization field and thus to a change of the local magnetic field (6-8), additional phase artifacts are introduced.To overcome these problems, several correction strategies have been proposed, such as respiratory gating (9), navigator echoes (10), multibaseline acquisition to sample periodic changes (11,12), and referenceless phase corrections (13). Furthermore, the concept of the equivalent...

Magnetic resonance imaging-guided high intensity focused ultrasound is a promising method for the noninvasive ablation of pathological tissue in abdominal organs such as liver and kidney. Due to the high perfusion rates of these organs, sustained sonications are required to achieve a sufficiently high temperature elevation to induce necrosis. However, the constant displacement of the target due to the respiratory cycle render continuous ablations challenging, since dynamic repositioning of the focal point is required. This study demonstrates subsecond 3D high intensity focused ultrasound-beam steering under magnetic resonance-guidance for the real-time compensation of respiratory motion. The target is observed in 3D space by coupling rapid 2D magnetic resonance-imaging with prospective slice tracking based on pencil-beam navigator echoes. The magnetic resonance-data is processed in real-time by a computationally efficient reconstruction pipeline, which provides the position, the temperature and the thermal dose on-the-fly, and which feeds corrections into the high intensity focused ultrasound-ablator. The effect of the residual update latency is reduced by using a 3D Kalman-predictor for trajectory anticipation. The suggested method is characterized with phantom experiments and verified in vivo on porcine kidney. The results show that for update frequencies of more than 10 Hz and latencies of less then 114 msec, temperature elevations can be achieved, which are comparable to static experiments. Magn Reson Med 64:1704-1712,

No abstract

Magnetic resonance (MR) guided high intensity focused ultrasound and external beam radiotherapy interventions, which we shall refer to as beam therapies/interventions, are promising techniques for the non-invasive ablation of tumours in abdominal organs. However, therapeutic energy delivery in these areas becomes challenging due to the continuous displacement of the organs with respiration. Previous studies have addressed this problem by coupling high-framerate MR-imaging with a tracking technique based on the algorithm proposed by Horn and Schunck (H and S), which was chosen due to its fast convergence rate and highly parallelisable numerical scheme. Such characteristics were shown to be indispensable for the real-time guidance of beam therapies. In its original form, however, the algorithm is sensitive to local grey-level intensity variations not attributed to motion such as those that occur, for example, in the proximity of pulsating arteries.In this study, an improved motion estimation strategy which reduces the impact of such effects is proposed. Displacements are estimated through the minimisation of a variation of the H and S functional for which the quadratic data fidelity term was replaced with a term based on the linear L(1)norm, resulting in what we have called an L(2)-L(1) functional.The proposed method was tested in the livers and kidneys of two healthy volunteers under free-breathing conditions, on a data set comprising 3000 images equally divided between the volunteers. The results show that, compared to the existing approaches, our method demonstrates a greater robustness to local grey-level intensity variations introduced by arterial pulsations. Additionally, the computational time required by our implementation make it compatible with the work-flow of real-time MR-guided beam interventions.To the best of our knowledge this study was the first to analyse the behaviour of an L(1)-based optical flow functional in an applicative context: real-time MR-guidance of beam therapies in moving organs.

Purpose: Immunotherapy promises unprecedented benefits to patients with cancer. However, the majority of cancer types, including high-risk neuroblastoma, remain immunologically unresponsive. High-intensity focused ultrasound (HIFU) is a noninvasive technique that can mechanically fractionate tumors, transforming immunologically ''cold'' tumors into responsive ''hot'' tumors.Experimental Design: We treated <2% of tumor volume in previously unresponsive, large, refractory murine neuroblastoma tumors with mechanical HIFU and assessed systemic immune response using flow cytometry, ELISA, and gene sequencing. In addition, we combined this treatment with aCTLA-4 and aPD-L1 to study its effect on the immune response and long-term survival.Results: Combining HIFU with aCTLA-4 and aPD-L1 significantly enhances antitumor response, improving survival from 0% to 62.5%. HIFU alone causes upregulation of splenic and lymph node NK cells and circulating IL2, IFNg, and DAMPs, whereas immune regulators like CD4 þ Foxp3 þ , IL10, and VEGF-A are significantly reduced. HIFU combined with checkpoint inhibitors induced significant increases in intratumoral CD4 þ , CD8a þ , and CD8a þ CD11c þ cells, CD11c þ in regional lymph nodes, and decrease in circulating IL10 compared with untreated group. We also report significant abscopal effect following unilateral treatment of mice with large, established bilateral tumors using HIFU and checkpoint inhibitors compared with tumors treated with HIFU or checkpoint inhibitors alone (61.1% survival, P < 0.0001). This combination treatment significantly also induces CD4 þ CD44 þhi CD62L þlow and CD8a þ CD44 þhi CD62L þlow population and is adoptively transferable, imparting immunity, slowing subsequent de novo tumor engraftment.Conclusions: Mechanical fractionation of tumors using HIFU can effectively induce immune sensitization in a previously unresponsive murine neuroblastoma model and promises a novel yet efficacious immunoadjuvant modality to overcome therapeutic resistance.