The presence of large number of false lesion classification on segmented brain MR images is a major problem in the accurate determination of lesion volumes in multiple sclerosis (MS) brains. In order to minimize the false lesion classifications, a strategy that combines parametric and nonparametric techniques is developed and implemented. This approach uses the information from the proton density (PD)-and T2-weighted and fluid attenuation inversion recovery (FLAIR) images. This strategy involves CSF and lesion classification using the Parzen window classifier. Image processing, morphological operations and ratio maps of PD and T2 weighted images are used for minimizing false positives. Contextual information is exploited for minimizing the false negative lesion classifications using hidden Markov random field -expectation maximization (HMRF-EM) algorithm. Lesions are delineated using fuzzy connectivity. The performance of this algorithm is quantitatively evaluated on 23 MS patients. Similarity index, percentages of over, under and correctestimations of lesions are computed by spatially comparing the results of present procedure with expert manual segmentation. The automated processing scheme detected 80% of the manually segmented lesions in the case of low-lesion load and 93% of the lesions in those cases with high lesion load.

Synopsis Proton magnetic resonance spectroscopy (1H-MRS) provides tissue metabolic information in vivo. This article reviews the role of MRS-determined metabolic alterations in lesions, normal appearing white matter, gray matter, and spinal cord in advancing our knowledge of pathological changes in multiple sclerosis (MS). In addition, the role of MRS in objectively evaluating therapeutic efficacy is reviewed. This potential metabolic information makes MRS a unique tool to follow MS disease evolution, understanding its pathogenesis, evaluating the disease severity, establishing a prognosis, and objectively evaluating the efficacy of therapeutic interventions.

A technique that involves minimal operator intervention was developed and implemented for identification and quantification of black holes on T1-weighted magnetic resonance images (T1 images) in multiple sclerosis (MS). Black holes were segmented on T1 images based on grayscale morphological operations. False classification of black holes was minimized by masking the segmented images with images obtained from the orthogonalization of T2-weighted and T1 images. Enhancing lesion voxels on postcontrast images were automatically identified and eliminated from being included in the black hole volume. Fuzzy connectivity was used for the delineation of black holes. The performance of this algorithm was quantitatively evaluated on 14 MS patients.

RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal models.METHODS: Europium (Eu3+)- doped cobalt ferrite (CF) dolutegravir (DTG)- loaded (EuCF-DTG) nanoparticles were synthesized then fully characterized based on their size, shape and stability. These were then used as platforms for nanoformulated drug biodistribution.RESULTS: Folic acid (FA) decoration of EuCF-DTG (FA-EuCF-DTG) nanoparticles facilitated macrophage targeting and sped drug entry across cell barriers. Macrophage uptake was higher for FA-EuCF-DTG than EuCF-DTG nanoparticles with relaxivities of r2 = 546 mM-1s-1 and r2 = 564 mM-1s-1 in saline, and r2 = 850 mM-1s-1 and r2 = 876 mM-1s-1 in cells, respectively. The values were ten or more times higher than what was observed for ultrasmall superparamagnetic iron oxide particles (r2 = 31.15 mM-1s-1 in saline) using identical iron concentrations. Drug particles were detected in macrophage Rab compartments by dual fluorescence labeling. Replicate particles elicited sustained antiretroviral responses. After parenteral injection of FA-EuCF-DTG and EuCF-DTG into rats and rhesus macaques, drug, iron and cobalt levels, measured by LC-MS/MS, magnetic resonance imaging, and ICP-MS were coordinate.CONCLUSION: We posit that these theranostic nanoprobes can assess LASER ART drug delivery and be used as part of a precision nanomedicine therapeutic strategy.

The size, shape and chemical composition of europium (Eu3+) cobalt ferrite (CFEu) nanoparticles were optimized for use as a “multimodal imaging nanoprobe” for combined fluorescence and magnetic resonance bioimaging. Doping Eu3+ ions into a CF structure imparts unique bioimaging and magnetic properties to the nanostructure that can be used for real-time screening of targeted nanoformulations for tissue biodistribution assessment. The CFEu nanoparticles (size ~7.2 nm) were prepared by solvothermal techniques and encapsulated into poloxamer 407-coated mesoporous silica (Si-P407) to form superparamagnetic monodisperse Si-CFEu nanoparticles with a size of ~ 140 nm. Folic acid (FA) nanoparticle decoration (FA-Si-CFEu, size ~ 140 nm) facilitated monocyte-derived macrophage (MDM) targeting. FA-Si-CFEu MDM uptake and retention was higher than seen with Si-CFEu nanoparticles. The transverse relaxivity of both Si-CFEu and FA-Si-CFEu particles were r2= 433.42 mM−1s−1 and r2= 419.52 mM−1s−1 (in saline) and r2= 736.57 mM−1s−1 and r2= 814.41 mM−1s−1 (in MDM), respectively. The results were greater than a log order-of-magnitude than what was observed at replicate iron concentrations for ultrasmall superparamagnetic iron oxide (USPIO) particles (r2= 31.15 mM−1s−1 in saline) and paralleled data sets obtained for T2 magnetic resonance imaging. We now provide a developmental opportunity to employ these novel particles for theranostic drug distribution and efficacy evaluations.