Chris Heyn

In vivo magnetic resonance imaging of single cells in mouse brain with optical validation.

In the current work we demonstrate, for the first time, that single cells can be detected in mouse brain in vivo using magnetic resonance imaging (MRI). Cells were labeled with superparamagnetic iron oxide nanoparticles and injected into the circulation of mice. Individual cells trapped within the microcirculation of the brain could be visualized with high‐resolution MRI using optimized MR hardware and the fast imaging employing steady state acquisition (FIESTA) pulse sequence on a 1.5 T clinical MRI scanner. Single cells appear as discrete signal voids on MR images. Direct optical validation was provided by coregistering signal voids on MRI with single cells visualized using high‐resolution confocal microscopy. This work demonstrates the sensitivity of MRI for detecting single cells in small animals for a wide range of application from stem cell to cancer cell tracking. Magn Reson Med, 2006.

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single‐cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single‐cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease. Magn Reson Med, 2006. Published 2006 Wiley‐Liss, Inc.

Imaging single mammalian cells with a 1.5 T clinical MRI scanner

In the present work, we demonstrate that the steady‐state free precession (SSFP) imaging pulse sequence FIESTA (fast imaging employing steady state acquisition) used in conjunction with a custom‐built insertable gradient coil and customized RF coils can be used to detect individual SPIO‐labeled cells using a commonly available 1.5 T clinical MRI scanner. This work provides the first evidence that single‐cell tracking will be possible using clinical MRI scanners, opening up new possibilities for cell tracking and monitoring of cellular therapeutics in vivo in humans. Magn Reson Med 49:968–971, 2003.

Detection Threshold of Single SPIO-Labeled Cells With FIESTA

MRI of superparamagnetic iron oxide (SPIO)‐labeled cells has become a valuable tool for studying the in vivo trafficking of transplanted cells. Cellular detection with MRI is generally considered to be orders of magnitude less sensitive than other techniques, such as positron emission tomography (PET), single photon emission‐computed tomography (SPECT), or optical fluorescence microscopy. However, an analytic description of the detection threshold for single SPIO‐labeled cells and the parameters that govern detection has not been adequately provided. In the present work, the detection threshold for single SPIO‐labeled cells and the effect of resolution and SNR were studied for a balanced steady‐state free precession (SSFP) sequence (3D‐FIESTA). Based on the results from both theoretical and experimental analyses, an expression that predicts the minimum detectable mass of SPIO (mc) required to detect a single cell against a uniform signal background was derived: mc = 5v/(Kfsl · SNR), where v is the voxel volume, SNR is the image signal‐to‐noise ratio, and Kfsl is an empirical constant measured to be 6.2 ± 0.5 × 10−5 μl/pgFe. Using this expression, it was shown that the sensitivity of MRI is not very different from that of PET, requiring femtomole quantities of SPIO iron for detection under typical micro‐imaging conditions (100 μm isotropic resolution, SNR = 60). The results of this work will aid in the design of cellular imaging experiments by defining the lower limit of SPIO labeling required for single cell detection at any given resolution and SNR. Magn Reson Med 53:312–320, 2005.

Quantification of cerebrovascular reactivity by blood oxygen level-dependent MR imaging and correlation with conventional angiography in patients with Moyamoya disease.

BACKGROUND AND PURPOSE: BOLD MR imaging combined with a technique for precision control of end-tidal pCO2 was used to produce quantitative maps of CVR in patients with Moyamoya disease. The technique was validated against measures of disease severity by using conventional angiography; it then was used to study the relationship between CVR, vascular steal, and disease severity. MATERIALS AND METHODS: A retrospective analysis comparing conventional angiography with BOLD MR imaging was performed on 11 patients with Moyamoya disease. Iso-oxic cycling of end-tidal pCO2 between 2 target values was performed during BOLD MR imaging. CVR was calculated as the BOLD signal difference per ΔpCO2. CVR was correlated with the presence of Moyamoya or pial collaterals and the degree of Moyamaya disease as graded by using a modified Suzuki score. RESULTS: A good correlation between mean CVR and Suzuki score was found for the MCA and ACA territories (Pearson correlation coefficient, −0.7560 and −0.6140, respectively; P < .0001). A similar correlation was found between mean CVR and the presence of pial and Moyamoya collateral vessels for combined MCA and ACA territories (Pearson correlation coefficient, −0.7466; P < .0001). On a voxel-for-voxel basis, there was a greater extent of steal within vascular territories with increasing disease severity (higher modified Suzuki score). Mean CVR was found to scale nonlinearly with the extent of vascular steal. CONCLUSIONS: Quantitative measures of CVR show direct correlation with impaired vascular supply as measured by the modified Suzuki score and enable direct investigation of the physiology of autoregulatory reserve, including steal phenomenon, within a given vascular territory.

Histologically Confirmed Hippocampal Structural Features Revealed by 3T MR Imaging: Potential to Increase Diagnostic Specificity of Mesial Temporal Sclerosis

BACKGROUND AND PURPOSE: With appropriate selection, temporal lobe epilepsy is potentially curable with surgical intervention achieving seizure freedom in ∼80% of individuals. MR imaging−based identification of MTS remains central to the selection process but currently relies on qualitative visual analysis. We sought to determine if new ultrastructural hippocampal details seen on 3T MR imaging had histopathologic correlates and whether these could serve as a useful tool in MTS identification. MATERIALS AND METHODS: Patients undergoing selective anterior temporal lobectomy (n = 5) were scanned using 3T MR imaging preoperatively. En bloc resections were rescanned and subsequently prepared for histopathologic analysis of all hippocampal layers in the CA1–3 regions. Using a newly identified landmark from 3T FSTIR coronal images in 20 patients with histologically confirmed MTS, blinded studies compared ipsilateral and contralateral sides to generate threshold measurements for application in a fast quantitative analysis tool. RESULTS: Histopathologic analysis and correlation with 3T imaging of en bloc resections identified the low-intensity signal as the stratum lacunosum. MTS was associated with extensive gliosis throughout the CA1–3 regions, with loss of tissue thickness in the stratum pyramidale most pronounced in CA1. Fast quantitative analysis by using the stratum lacunosum as a landmark provided a test that identifies MTS with a SN of 70% and SP of 85%. CONCLUSIONS: Here we delineated ultrastructural hippocampal details seen on 3T MR imaging in both the in vivo and ex vivo setting, correlating these with histopathologic features consistent with MTS, and provided preliminary data suggesting their utility in the development of a quantitative analysis assessment tool for application in surgical-candidate selection.

Longitudinal quantitative MRI in multiple system atrophy and progressive supranuclear palsy

OBJECTIVE MRI has been used in parkinsonism to assess atrophy, tissue water diffusivity, and mineral deposition but usually at a single time-point. However, multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are progressive diseases. This study assessed the value of longitudinal MRI in characterizing the time course of the degenerative process. METHODS Two serial MRIs (mean 23 months apart) were retrospectively analyzed in 12 MSA, 6 PSP, and 18 age and sex matched controls. Assessment included selected cross-sectional areas, regional apparent diffusion coefficient (ADC) and gradient echo (GRE) intensity ratios of the lateral ventricles, caudate, putamen, middle cerebellar peduncle, pons and midbrain. RESULTS On follow-up imaging, there was a larger ADC increase in the putamen in PSP over time compared to controls (p = 0.02). In MSA there was greater volume loss in the pons over time compared to controls (p = 0.002). In MSA the changes in middle cerebellar peduncle ADC were correlated with motor symptom severity according to the Unified Parkinsons Disease Rating Scale Part III (p = 0.005). CONCLUSIONS Evidence of progressive neurodegeneration can be observed on MRI in MSA and PSP within two years consisting of increasing putaminal ADC in PSP and pontine atrophy in MSA.

MRI of the pancreas: Problem solving tool

Advances in MR hardware and pulse sequence design over the years have improved the quality and robustness of MR imaging of the pancreas. Today, MRI is an indispensible tool for studying the pancreas and can provide useful information not attainable with other noninvasive or minimally invasive imaging techniques. In the present review, specific cases are reviewed where the strengths of MRI demonstrate the utility of this imaging modality as a problem solving tool. J. Magn. Reson. Imaging 2012;36:1037–1051.

Re-irradiation of Vertebral Body Metastases: Treatment in the Radiosurgery Era

Vertebral bodies remain one of the most common sites of metastases. In cases where surgical intervention is not indicated or appropriate, conventional external radiation therapy (cEBRT) has been the standard treatment modality. Unfortunately, cEBRT is typically limited, with low complete response and poor local control rates. Disappointing results with re-irradiation using cEBRT highlight the need for innovative salvage therapeutic strategies, such as stereotactic body radiotherapy. A detailed description of this complex treatment strategy is outlined, as is a systematic review of current literature. Although data are limited to single institution series, re-irradiation has consistently been found to be effective with respect to local control (1 year rates range from 66 to 90%) and pain response. Importantly, the treatment is shown to be safe, with the crude rate of radiation myelopathy <1% and a rate of vertebral compression fracture of 12%. As further research and technologic advances continue to refine therapy, stereotactic body radiotherapy is now a recommended option for the treatment of previously irradiated vertebral body metastases.

High Speed, High Density Intraoperative 3D Optical Topographical Imaging with Efficient Registration to MRI and CT for Craniospinal Surgical Navigation

Intraoperative image-guided surgical navigation for craniospinal procedures has significantly improved accuracy by providing an avenue for the surgeon to visualize underlying internal structures corresponding to the exposed surface anatomy. Despite the obvious benefits of surgical navigation, surgeon adoption remains relatively low due to long setup and registration times, steep learning curves, and workflow disruptions. We introduce an experimental navigation system utilizing optical topographical imaging (OTI) to acquire the 3D surface anatomy of the surgical cavity, enabling visualization of internal structures relative to exposed surface anatomy from registered preoperative images. Our OTI approach includes near instantaneous and accurate optical measurement of >250,000 surface points, computed at >52,000 points-per-second for considerably faster patient registration than commercially available benchmark systems without compromising spatial accuracy. Our experience of 171 human craniospinal surgical procedures, demonstrated significant workflow improvement (41 s vs. 258 s and 794 s, p < 0.05) relative to benchmark navigation systems without compromising surgical accuracy. Our advancements provide the cornerstone for widespread adoption of image guidance technologies for faster and safer surgeries without intraoperative CT or MRI scans. This work represents a major workflow improvement for navigated craniospinal procedures with possible extension to other image-guided applications.