A convolutional neural network to filter artifacts in spectroscopic MRI

Purpose Proton MRSI is a noninvasive modality capable of generating volumetric maps of in vivo tissue metabolism without the need for ionizing radiation or injected contrast agent. Magnetic resonance spectroscopic imaging has been shown to be a viable imaging modality for studying several neuropathologies. However, a key hurdle in the routine clinical adoption of MRSI is the presence of spectral artifacts that can arise from a number of sources, possibly leading to false information. Methods A deep learning model was developed that was capable of identifying and filtering out poor quality spectra. The core of the model used a tiled convolutional neural network that analyzed frequency‐domain spectra to detect artifacts. Results When compared with a panel of MRS experts, our convolutional neural network achieved high sensitivity and specificity with an area under the curve of 0.95. A visualization scheme was implemented to better understand how the convolutional neural network made its judgement on single‐voxel or multivoxel MRSI, and the convolutional neural network was embedded into a pipeline capable of producing whole‐brain spectroscopic MRI volumes in real time. Conclusion The fully automated method for assessment of spectral quality provides a valuable tool to support clinical MRSI or spectroscopic MRI studies for use in fields such as adaptive radiation therapy planning

Inhibition of the CXCL12/CXCR4-axis as preventive therapy for radiation-induced pulmonary fibrosis

Background: A devastating late injury caused by radiation is pulmonary fibrosis. This risk may limit the volume of irradiation and compromise potentially curative therapy. Therefore, development of a therapy to prevent this toxicity can be of great benefit for this patient population. Activation of the chemokine receptor CXCR4 by its ligand stromal cell-derived factor 1 (SDF-1/CXCL12) may be important in the development of radiation-induced pulmonary fibrosis. Here, we tested whether MSX-122, a novel small molecule and partial CXCR4 antagonist, can block development of this fibrotic process. Methodology/Principal Findings: The radiation-induced lung fibrosis model used was C57BL/6 mice irradiated to the entire thorax or right hemithorax to 20 Gy. Our parabiotic model involved joining a transgenic C57BL/6 mouse expressing GFP with a wild-type mouse that was subsequently irradiated to assess for migration of GFP+ bone marrow-derived progenitor cells to the irradiated lung. CXCL12 levels in the bronchoalveolar lavage fluid (BALF) and serum after irradiation were determined by ELISA. CXCR4 and CXCL12 mRNA in the irradiated lung was determined by RNase protection assay. Irradiated mice were treated daily with AMD3100, an established CXCR4 antagonist; MSX-122; and their corresponding vehicles to determine impact of drug treatment on fibrosis development. Fibrosis was assessed by serial CTs and histology. After irradiation, CXCL12 levels increased in BALF and serum with a corresponding rise in CXCR4 mRNA within irradiated lungs consistent with recruitment of a CXCR4+ cell population. Using our parabiotic model, we demonstrated recruitment of CXCR4+ bone marrow-derived mesenchymal stem cells, identified based on marker expression, to irradiated lungs. Finally, irradiated mice that received MSX-122 had significant reductions in development of pulmonary fibrosis while AMD3100 did not significantly suppress this fibrotic process. Conclusions/Significance: CXCR4 inhibition by drugs such as MSX-122 may alleviate potential radiation-induced lung injury, presenting future therapeutic opportunities for patients requiring chest irradiation. © 2013 Shu et al

Investigations of the water oxidation complex in PS II

In this thesis an attempt was made to take the water oxidizing complex apart in a controlled way and to reconstitute it to its functional form.The mechanism of photosynthetic water oxidation has been probed by the use of the substrate analogue NH\sb2OH in 1 M NaCl treated PSII membranes lacking the 17 and 23 kD extrinsic proteins. A plot of the Mn released versus (NH\sb2OH) shows a sigmoidal shape. The results were interpreted in terms of a cooperativity model. The plot of Mn release versus oxygen evolving activity shows that all 4 Mn in the reaction center are essential for active oxygen evolution.1 M CaCl\sb2 treated PSII membranes, which lack all 3 extrinsic polypeptides (17, 23, and 33 kD) have low oxygen evolving activity in spite of the full complement of 4 Mn per reaction center. If the light intensity is sufficiently low, 1 M CaCl\sb2 treated PSII evolve the same number of oxygen molecules per photon as 1 M NaCl treated PSII. Therefore, removal of the 33 kD polypeptide did not inactivate the Mn center and all Mn centers are intact. When the light intensity is high, there is possible alternative electron donors to P\sb{680}\sp{+} in 1 M CaCl\sb2 treated PSII (e.g., Chl). As a result, the fluorescence and the oxygen evolving activity are low. I analyzed the fluorescence data of the S\sb1 $\to$ S\sb2 transition in DCMU-treated samples. The transition time of CaCl\sb2 PSII is 1.4 times longer than that of NaCl PSII. This slow-down of the S\sb1 $\to$ S\sb2transition rate is not the main reason for slow donor side and there are other reports that indicate the slow-down of the S\sb3 $\to$ S\sb0 transition rate. It is likely that other S state transitions, including the dark reaction, are slowed down as well.I reconstituted 37% of the oxygen evolving activity with 40% Mn concentration in the reconstituted sample. Therefore, about 40% of the centers have all 4 Mn while the other 60% of the centers have no Mn. It is very plausible that Mn rebinding also involves cooperativity. Other divalent transition metals like Fe\sp{2+} and Co\sp{2+} apparently compete for the Mn binding sites and may form mixed metal clusters.U of I OnlyETDs are only available to UIUC Users without author permissio

Quantitative Methods in Brain Tumor Imaging

Magnetic resonance imaging (MRI) has an important role to play in the care of patients with brain injury or disease, but other forms of clinical imaging are also useful. For cancer patients, MRI is often used in initial diagnosis, treatment planning, and continued follow-up. Here, the many variations of MRI, from contrast-enhanced T1-weighted, diffusion-weighted, perfusion-weighted, magnetic resonance spectroscopy, and other data collection methods provide MRI with the ability to highlight many different physiologic and metabolic properties of cancer. Quantitative methods in brain imaging have the ability to guide physicians as they work with patients to make clinical decisions about their care. This chapter will focus on the use of MRI in the detection, diagnosing, staging, and therapy monitoring of brain tumors, but reference to other imaging methods in the brain is also noted

Eliminating the Heart from the Curcumin Molecule: Monocarbonyl Curcumin Mimics (MACs)

Curcumin is a natural product with several thousand years of heritage. Its traditional Asian application to human ailments has been subjected in recent decades to worldwide pharmacological, biochemical and clinical investigations. Curcumin’s Achilles heel lies in its poor aqueous solubility and rapid degradation at pH ~ 7.4. Researchers have sought to unlock curcumin’s assets by chemical manipulation. One class of molecules under scrutiny are the monocarbonyl analogs of curcumin (MACs). A thousand plus such agents have been created and tested primarily against cancer and inflammation. The outcome is clear. In vitro, MACs furnish a 10–20 fold potency gain vs. curcumin for numerous cancer cell lines and cellular proteins. Similarly, MACs have successfully demonstrated better pharmacokinetic (PK) profiles in mice and greater tumor regression in cancer xenografts in vivo than curcumin. The compounds reveal limited toxicity as measured by murine weight gain and histopathological assessment. To our knowledge, MAC members have not yet been monitored in larger animals or humans. However, Phase 1 clinical trials are certainly on the horizon. The present review focuses on the large and evolving body of work in cancer and inflammation, but also covers MAC structural diversity and early discovery for treatment of bacteria, tuberculosis, Alzheimer’s disease and malaria

Mapping early tumor response to radiotherapy using diffusion kurtosis imaging

Purpose In this pilot study, DKI measures of diffusivity and kurtosis were compared in active tumor regions and correlated to radiologic response to radiotherapy after completion of 2 weeks of treatment to derive potential early measures of tumor response. Methods MRI and Magnetic Resonance Spectroscopic Imaging (MRSI) data were acquired before the beginning of RT (pre-RT) and 2 weeks after the initiation of treatment (during-RT) in 14 glioblastoma patients. The active tumor region was outlined as the union of the residual contrast-enhancing region and metabolically active tumor region. Average and standard deviation of mean, axial, and radial diffusivity (MD, AD, RD) and mean, axial, and radial kurtosis (MK, AK, RK) values were calculated for the active tumor VOI from images acquired pre-RT and during-RT and paired t-tests were executed to estimate pairwise differences. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive capabilities of changes in diffusion metrics for progression-free survival (PFS). Results Analysis showed significant pairwise differences for AD (p = 0.035; Cohen’s d of 0.659) and AK (p = 0.019; Cohen’s d of 0.753) in diffusion measures after 2 weeks of RT. ROC curve analysis showed that percentage change differences in AD and AK between pre-RT and during-RT scans provided an Area Under the Curve (AUC) of 0.524 and 0.762, respectively, in discriminating responders (PFS>180 days) and non-responders (PFS<180 days). Conclusion This pilot study, although preliminary in nature, showed significant changes in AD and AK maps, with kurtosis derived AK maps showing an increased sensitivity in mapping early changes in the active tumor regions