Samuel Barnes

Susceptibility-weighted imaging: clinical angiographic applications.

By combining filtered phase and magnitude information to create a novel and intrinsic source of contrast, susceptibility-weighted imaging (SWI) has shown great promise in clinical angiography and venography. SWI has contributed to new insights into traumatic brain injury, the role of calcification in atherosclerosis, and the possible relationship between blood settling and deep venous thrombosis. A further contribution from SWI to deep venous thrombosis research (and also stroke) involves its application to the noninvasive measurement of oxygen saturation in the brain and in other tissues. Altogether, SWI offers manifold and diverse avenues for further research using angiographic and venographic techniques.

Semiautomated detection of cerebral microbleeds in magnetic resonance images.

Cerebral microbleeds (CMBs) are increasingly being recognized as an important biomarker for neurovascular diseases. So far, all attempts to count and quantify them have relied on manual methods that are time-consuming and can be inconsistent. A technique is presented that semiautomatically identifies CMBs in susceptibility weighted images (SWI). This will both reduce the processing time and increase the consistency over manual methods. This technique relies on a statistical thresholding algorithm to identify hypointensities within the image. A support vector machine (SVM) supervised learning classifier is then used to separate true CMB from other marked hypointensities. The classifier relies on identifying features such as shape and signal intensity to identify true CMBs. The results from the automated section are then subject to manual review to remove false-positives. This technique is able to achieve a sensitivity of 81.7% compared with the gold standard of manual review and consensus by multiple reviewers. In subjects with many CMBs, this presents a faster alternative to current manual techniques at the cost of some lost sensitivity.

Imaging the Vessel Wall in Major Peripheral Arteries using Susceptibility Weighted Imaging

To demonstrate a novel contrast mechanism for imaging the vessel wall and vessel wall calcification using susceptibility‐weighted imaging (SWI).

Susceptibility-weighted imaging in the experimental autoimmune encephalomyelitis model of multiple sclerosis indicates elevated deoxyhemoglobin, iron deposition and demyelination

Background: Susceptibility-weighted imaging (SWI) is an iron-sensitive magnetic resonance imaging (MRI) method that has shown iron-related lesions in multiple sclerosis (MS) patients. The contribution of deoxyhemoglobin to the signals seen in SWI has not been well characterized in MS. Objectives: To determine if SWI lesions (seen as focal hypointensities) exist in the experimental autoimmune encephalomyelitis (EAE) animal model of MS, and to determine whether the lesions relate to iron deposits, inflammation, demyelination, and/or deoxyhemoglobin in the vasculature. Methods: We performed SWI on the lumbar spinal cord and cerebellum of EAE and control mice (both complete Freund’s adjuvant/pertussis toxin (CFA/PTX)-immunized and naive). We also performed SWI on mice before and after perfusion (to remove blood from vessels). SWI lesions were counted and their locations were compared to histology for iron, myelin and inflammation. Results: SWI lesions were found to exist in the EAE model. Many lesions seen by SWI were not present after perfusion, especially at the grey/white matter boundary of the lumbar spinal cord and in the cerebellum, indicating that these lesion signals were associated with deoxyhemoglobin present in the lumen of vessels. We also observed SWI lesions in the white matter of the lumbar spinal cord that corresponded to iron deposition, inflammation and demyelination. In the cerebellum, SWI lesions were present in white matter tracts, where we found histological evidence of inflammatory perivascular cuffs. Conclusions: SWI lesions exist in EAE mice. Many lesions seen in SWI were a result of deoxyhemoglobin in the blood, and so may indicate areas of hypoxia. A smaller number of SWI lesions coincided with parenchymal iron, demyelination, and/or inflammation.

Iron quantification of microbleeds in postmortem brain.

Brain microbleeds (BMB) are associated with chronic and acute cerebrovascular disease and present a source of pathologic iron to the brain proportional to extravasated blood. Therefore, BMB iron content is potentially a valuable biomarker. We tested noninvasive phase image methods to quantify iron content and estimate true source diameter (i.e., unobscured by the blooming effect) of BMB in postmortem human tissue. Tissue slices containing BMB were imaged using a susceptibility weighted imaging protocol at 11.7T. BMB lesions were assayed for iron content using atomic absorption spectrometry. Measurements of geometric features in phase images were related to lesion iron content and source diameter using a mathematical model. BMB diameter was estimated by image feature geometry alone without explicit relation to the magnetic susceptibility. A strong linear relationship (R2 = 0.984, P < 0.001) predicted by theory was observed in the experimental data, presenting a tentative standardization curve where BMB iron content in similar tissues could be calculated. In addition, we report BMB iron mass measurements, as well as upper bound diameter and lower bound iron concentration estimates. Our methods potentially allows the calculation of brain iron load indices based on BMB iron content and classification of BMB by size unobscured by the blooming effect. Magn Reson Med, 2011.

Proton beam scattering system optimization for clinical and research applications

PURPOSE To develop and test a method for optimizing and constructing a dual scattering system in passively scattered proton therapy. METHODS A beam optics optimization algorithm was developed to optimize the thickness of the first scatterer (S1) and the profile (of both the high-Z material and Lexan) of the second scatterer (S2) to deliver a proton beam matching a given set of parameters, including field diameter, fluence, flatness, and symmetry. A new manufacturing process was also tested that allows the contoured second scattering foil to be created much more economically and quickly using Cerrobend casting. Two application-specific scattering systems were developed and tested using both experimental and Monte Carlo techniques to validate the optimization process described. RESULTS A scattering system was optimized and constructed to deliver large uniform irradiations of radiobiology samples at low dose rates. This system was successfully built and tested using film and ionization chambers. The system delivered a uniform radiation field of 50 cm diameter (to a dose of ± 7% of the central axis) while the depth dose profile could be tuned to match the specifications of the particular investigator using modulator wheels and range shifters. A second scattering system for intermediate field size (4 cm < diameter < 10 cm) stereotactic radiosurgery and radiation therapy (SRS and SRT) treatments was also developed and tested using GEANT4. This system improved beam efficiency by over 70% compared with existing scattering systems while maintaining field flatness and depth dose profile. In both cases the proton range uniformity across the radiation field was maintained, further indicating the accuracy of the energy loss formalism in the optimization algorithm. CONCLUSIONS The methods described allow for rapid prototyping of scattering foils to meet the demands of both research and clinical beam delivery applications in proton therapy.

Settling properties of venous blood demonstrated in the peripheral vasculature using susceptibility-weighted imaging (SWI)

To evaluate the settling properties of venous blood in the peripheral vasculature during periods of immobility.

In Vivo Iron Quantification in Collagenase-Induced Microbleeds in Rat Brain

Brain microbleeds (BMB) are associated with chronic and acute cerebrovascular disease. Because BMB present in the brain is a source of potentially cytotoxic iron proportional to the volume of extravasated blood, BMB iron content is a potentially valuable biomarker both to assess tissue risk and small cerebral vessel health. We recently reported methods to quantify focal iron sources using phase images that were tested in phantoms and BMB in postmortem tissue. In this study, we applied our methods to small hemorrhagic lesions induced in the in vivo rat brain using bacterial collagenase. As expected by theory, measurements of geometric features in phase images correlated with lesion iron content measured by graphite furnace atomic absorption spectrometry. Iron content estimation following BMB in an in vivo rodent model could shed light on the role and temporal evolution of iron‐mediated tissue damage and efficacy of potential treatments in cerebrovascular diseases associated with BMB. Magn Reson Med, 2012.

Imaging the vessel wall in major peripheral arteries using susceptibility weighted imaging: visualizing calcifications

Introduction: Magnetic resonance imaging (MRI) has been used for many years to study atherosclerosis. Black blood techniques are the most ubiquitous and are used to suppress the signal from flowing blood, making the vessel wall more conspicuous. The purpose of this study was to demonstrate a novel approach to imaging the vessel wall and vessel wall calcification using susceptibility weighted imaging (SWI) with no need to suppress the signal from the blood. Methods: Optimizing the imaging parameters: The SWI sequence parameters were optimized to allow for the best visualization of the femoral artery lumen in the magnitude images and the arterial wall in the phase images. Parameters such as resolution (for time considerations), flip angle (for contrast in the magnitude images) and echo time (for phase contrast) were considered. Vessel wall magnitude and phase measurements: ROIs from the top to the bottom of the visible portions of the femoral artery were taken. The lumen SNR and muscle SNR were calculated on both magnitude and phase images. The contrast-to-noise ratio of vessel wall/lumen and vessel wall/muscle was also calculated. Patients study: A series of 18 subjects were imaged with multi-detector computed tomography (MDCT) and high resolution susceptibility weighted imaging (SWI) at 3T. Calcification Measurements: The area of calcification was manually measured on CT images and MR images (both magnitude and phase images) by an experienced radiologist. SPIN software (Detroit, MI) was used to interpolate the images by a factor of 4 and measure the calcifications. The correlation of calcification area (CA) between CT and MR images was performed and a Pearson correlation coefficient calculated. The agreement of CA measurements by MR and CT was assessed by using the Bland and Altman plot. Results: The optimal choice of imaging parameters was found to be: TE = 15.6 ms (in-phase for fat); TR = 25 ms, FA = 10, BW = 80 Hz/pixel, resolution = 0.5mm x 0.5mm in-plane and 1.0mm through-plane, with an acquisition matrix of 512 x 384 x 64 (for read, phase and slice-select direction) and a total scan time of 8 minutes. Figure 1 shows an example image of normal arterial and vessel wall in both magnitude and phase. The magnitude contrast-to-noise ratio (CNR) between artery and vessel wall was 12:1. The phase CNR between the arterial wall and the lumen was 7:1. A total of 19 calcifications in the femoral vessel wall were identified with SWI in 8 subjects. The mean area of calcification measured on CT, magnitude and phase images was 0.37±0.17cm, 0.29±0.13 cm, 0.38±0.18cm respectively. The Pearson correlation coefficient of the measured lesion area between CT and magnitude image is 0.85 (p<0.001); between CT and phase image is 0.92 (p<0.001). A typical case having popliteal artery calcification is shown in Figure 2. Both magnitude and phase images show the calcifications clearly in the popliteal artery wall and correlate well with the CT image. Conclusions: SWI offers a means to image a large field-of-view over which the arterial wall can be clearly seen in both magnitude and SWI filtered phase images. These lesions were seen in CT and SWI and correlated well in both size and position with both methods. We anticipate that SWI will play a complementary role to the current multi-contrast approach in studying atherosclerosis. Reference: 1.Yuan C, Kerwin WS. JMRI 2004:19:710-719. 2.Haacke EM, Xu Y, Cheng YC, Reichenbach JR. MRM 2004;52:612-618.

Acoustically modulated magnetic resonance imaging of gas-filled protein nanostructures

Non-invasive biological imaging requires materials capable of interacting with deeply penetrant forms of energy such as magnetic fields and sound waves. Here, we show that gas vesicles (GVs), a unique class of gas-filled protein nanostructures with differential magnetic susceptibility relative to water, can produce robust contrast in magnetic resonance imaging (MRI) at sub-nanomolar concentrations, and that this contrast can be inactivated with ultrasound in situ to enable background-free imaging. We demonstrate this capability in vitro, in cells expressing these nanostructures as genetically encoded reporters, and in three model in vivo scenarios. Genetic variants of GVs, differing in their magnetic or mechanical phenotypes, allow multiplexed imaging using parametric MRI and differential acoustic sensitivity. Additionally, clustering-induced changes in MRI contrast enable the design of dynamic molecular sensors. By coupling the complementary physics of MRI and ultrasound, this nanomaterial gives rise to a distinct modality for molecular imaging with unique advantages and capabilities.Gas-filled vesicles derived from photosynthetic microbes are shown to elicit magnetic resonance imaging contrast in vitro and in vivo with the potential for acoustically modulated multiplexing and molecular sensing.