Recent Patents on Medical Imaging (Discontinued) - Volume 1, Issue 2, 2011

Identification of Metaphase-II (M-II) chromosomes in living human oocytes is very important when performing intracytoplasmic sperm injection (ICSI) or nuclear transfer as has been reported in several studies and registered in some recent patents that we reviewed. However, until now studies of the M-II chromosomes have been substituted by studies of the M-II spindle because of lack of visualization of the M-II chromosomes. We developed a new method for the visualization of the M-II chromosomes that has a success rate above 90% without the use of any stains or optic devices. It is now possible to perform ICSI with a lower risk of damaging M-II chromosomes. This technique increases the potential for embryonic development resulting in a better clinical outcome, and is expected to contribute to the rescuing of the advance oocytes and mitochondrial disease following the nuclear transfer.

Recent patents show that ultrahigh Magnetic field, Nuclear Magnetic Resonance (NMR) microscopy is emerging as bioimaging tool to study metabolic events and protein structure-functional characterization in the small animals and pure proteins in solutions. 900 MHz NMR magnet design characteristics were reviewed and imaging was done for high resolution rat skin, heart, mice kidney using NMR microscopy technique. Superparamagnetic iron-oxide bound avidin-polystyrene coated with anti-troponin (SPIOT) nanoparticles as imaging contrast agent was used to enhance contrast. 900 MHz NMR microscopy provides structural microscopic details and can detect the nanoparticle targeted heart muscle fiber orientation by deposits of nanoparticles. 900 MHz microscopy was done for imaging phantom, heart, skin, kidneys. Anti-troponin was bound with polymer coated avidin-iron oxide complex to inject in rat to image the excised heart. Fast spin echo and fast gradient echo imaging techniques were used for T2-weighted rat heart. After imaging, rat hearts were processed for histology. First time available 900 MHz NMR system was more suitable for longer data acquisition at room temperature with enhanced SNR, MR signal intensity, and high resolution in less time. The imager generated skin, kidney, and heart images with visible muscle fiber orientation and comparable with histology details. The present paper is an overview with available patents on 900 MHz NMR spectrometer to convert into microscopic imager to generate high MR signal intensity and high resolution images with possibility on 1000 MHz field. The imager was a suitable research tool for microscopy, protein structural characterization and drug therapeutic monitoring.

There are a variety of tissues in the musculoskeletal [MSK] system, such as menisci, ligaments, tendons, entheses, cortical and trabecular bone, which cannot be imaged with conventional magnetic resonance [MR] imaging sequences because of their short T2 relaxation times. We report a recent patent on ultrashort TE spectroscopic imaging [UTESI] which can be used to provide high resolution imaging as well as quantitative evaluation of the short T2 tissues in the MSK systems in vitro and in vivo. The recent patents on spectroscopic imaging and UTE imaging are also reviewed.

The application of tissue Doppler imaging (TDI) has shown remarkable growth in clinical practice during the past few years, especially, in risk stratification of patients with coronary heart disease or heart failure (systolic and diastolic). Previous patents have showed the role of TDI to assess hemodynamic parameters. TDI systolic velocities have been used to detect impaired systolic function in patient with coronary artery disease and heart failure. The clinical utility of TDI as a tool for calculating Myocardial Performance Index (MPI) in comparison with the conventional method has already demonstrated. More recently, cardiac time intervals by TDI have also been found as new applications in diagnosing left ventricle dysfunction.

Advances in the area of three-dimensional (3D) ultrasound in the last five years have led to the development of several types of software some of which have proven to be of clinical utility in prenatal diagnosis. The Multi Extended Imaging (3DMXI) is a recently developed software available on Accuvix V20 Prestige equipments (Medison, Seoul, Korea). It consists of three programs: Multi Volume Slice, Mirror View and Multi OVIX (Oblique View eXtended). Because it has only been commercially available since 2009, there are no publications on its use in the field of obstetrics. This patent review highlights developments in this area in the past few years, focusing on new software Multi Extended Imaging (3DMXI) and describes its possible clinical applications in the field of diagnostic obstetrical imaging.

Productivity in the drug discovery and development process has seen a drastic decline over the last few years. Clearly, traditional approaches to drug development are not working. The new concept called “microdosing studies” was recently announced as a promising methodology for accreting drug development. The microdosing studies is a concept by administrating a low dose (microdose) of a candidate compound to human volunteers to obtain in vivo human pharmacokinetic (PK) data at an early stage of drug development. As a result unpromising candidate drugs can be eliminated at an earlier stage of drug development. A key component for this concept is highly sensitive analytical methods such as positron emission tomography (PET), accelerator mass spectrometry (AMS) and liquid chromatography-mass spectrometry (LC/MS/MS). This issue focuses on PET methodology from basic to future prospects for drug development and patents related to it.

Integration of imaging data with immunohistology is a new art. Increased PET and MRI image intensities on rat breast tumor MRI-PET images were reviewed for possible correlation with tumor histology and MALDI imaging tumor characteristics in the light of recent inventions and patents. Increased signal intensities of intracellular (IC) sodium μMRI and flouro-2-deoxy-glucose utilization by μPET from apoptosis protein rich MALDI visible regions of tumors were positively correlated to chemosensitivity of Taxotere. MCF-7 cancer cell line induced rat tumor MRI-PET images and histology digital images were compared for correlation in pre- and post taxotere treated tumors. For MALDI imaging, iterated protein ion mass spectrometry peak analysis was done using data from laser raster over tumor slices in sequence and 3D tumor volume was simulated for specific peak(s) distribution. A criterion was developed to evaluate malignancy by histology and MRI-PET imaging. For correlation, regression analysis was done using MRI-PET imaging, histology and MALDI imaging data from MCF-7 tumor after 24 hours post-taxotere treatment. Apoptosis indices were calculated by histostaining using pentachrome, feulgen and ss-DNA antibody assay. Review showed sodium MRI and PET signal intensity distribution comparable and measurable in tumor tissue regions. In tumors, taxotere induced an increase in IC-Na MRI signal with decreased tumor size and micro-PET showed FDG uptake increase with decreased tumor size than that of control tumors after 24 hours. Histology features indicated tumor risk (high ‘IC/EC ratio’, high mitotic index and apoptotic index), decreased tumor viability (reduced mitotic figures, reduced diploidy or aneuploidy and proliferation index) after Taxotere treatment. These features in co-registered IC-Na, μPET hypermetabolic and monoclonal antibody (ss-DNA) sensitive regions showed 6% difference. MALDI imaging showed tumor specific protein ion species and their distribution showed empirical correlation (limited visual match) with MRI-PET signal intensities but comparable match with histology features. Recent patents strongly suggest the possibility of sodium MRI and PET multimodal imaging integrated with MALDI-imaging as an non-invasive chemosensitivity assay to monitor the anticancer effect.

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