Non-invasive Quantitative Technique Research Articles

Nuclear magnetic resonance studies of organic-inorganic composite solid electrolytes

Solid electrolytes have received widespread attention due to their higher safety than liquid electrolytes in the past decades. In particular, organic-inorganic composite solid electrolytes (CSEs) in which inorganic fillers dispersed in polymer solid electrolytes are considered to be one of the most promising candidate electrolytes for high-performance solid-state lithium batteries. Understanding the local environments and the conduction pathway/dynamics of Li+ is essential for the design of high-performance CSEs. Nuclear magnetic resonance (NMR) is a non-invasive quantitative technique that has unique capabilities in providing molecular structure information, morphological evolution, and measuring the movement of ions at different time scales. Therefore, for battery researchers, an accurate and comprehensive understanding of the basic principles and experimental design of solid-state NMR (SSNMR) is of great significance for investigating the abundant molecular structure and dynamics information in CSEs. The specific applications of the SSNMR technique in CSEs are briefly introduced in this present review.

The Value of Imaging and Composition-Based Biomarkers in Duchenne Muscular Dystrophy Clinical Trials.

As the drug development pipeline for Duchenne muscular dystrophy (DMD) rapidly advances, clinical trial outcomes need to be optimized. Effective assessment of disease burden, natural history progression, and response to therapy in clinical trials for Duchenne muscular dystrophy are critical factors for clinical trial success. By choosing optimal biomarkers to better assess therapeutic efficacy, study costs and sample size requirements can be reduced. Currently, functional measures continue to serve as the primary outcome for the majority of DMD clinical trials. Quantitative measures of muscle health, including magnetic resonance imaging and spectroscopy, electrical impedance myography, and ultrasound, sensitively identify diseased muscle, disease progression, and response to a therapeutic intervention. Furthermore, such non-invasive techniques have the potential to identify disease pathology prior to onset of clinical symptoms. Despite robust supportive evidence, non-invasive quantitative techniques are still not frequently utilized in clinical trials for Duchenne muscular dystrophy. Non-invasive quantitative techniques have demonstrated the ability to quantify disease progression and potential response to therapeutic intervention, and should be used as a supplement to current standard functional measures. Such methods have the potential to significantly accelerate the development and approval of therapies for DMD.

Dynamic light scattering spectroscopy of the retina-a non-invasive quantitative technique to objectively document visual improvement following ocular stem cell treatment.

A major difficulty in retinal research is the lack of a sensitive and quantitative method to objectively determine the functional ability of the retina. Dynamic light scattering (DLS) spectroscopy is a non-invasive quantitative technique that measures the thermal random motion of particles. DLS technology has been used to predict cataractogenesis in rabbits and detect and monitor diabetes mellitus in humans. The results demonstrated the utility of DLS to noninvasively quantitate subtle changes at the molecular level. The Stem Cell Ophthalmology Treatment Study is an Institutional Review Board (IRB) approved clinical study and the largest ophthalmology stem cell study to date. A DLS system has been developed to perform retinal measurements. Using this device, sequential measurements were made in a patient with nonarteritic ischemic optic neuropathy (NAION) who underwent stem cell treatment in the Stem Cell Ophthalmology Treatment Study. The patient demonstrated visual acuity and visual field improvements in the absence of observed changes in his fundus or in ocular coherence tomography examinations. Measurements with the DLS device showed significant increases in the diffusion coefficient. The DLS results identified changes that anticipated the improvements in central and peripheral vision for the patient. DLS has been demonstrated to have value in the early detection of molecular responses to interventions involving the retina and appears predictive of improvement in vision following stem cell treatment, irrespective of other imaging studies.

In Vivo Visualization of Stromal Macrophages via label-free FLIM-based metabolite imaging.

Macrophage infiltration and recruitment in breast tumors has been correlated with poor prognosis in breast cancer patients and has been linked to tumor cell dissemination. Much of our understanding comes from animal models in which macrophages are labeled by expression of an extrinsic fluorophore. However, conventional extrinsic fluorescence labeling approaches are not readily applied to human tissue and clinical use. We report a novel strategy that exploits endogenous fluorescence from the metabolic co-factors NADH and FAD with quantitation from Fluorescence Lifetime Imaging Microscopy (FLIM) as a means to non-invasively identify tumor-associated macrophages in the intact mammary tumor microenvironment. Macrophages were FADHI and demonstrated a glycolytic-like NADH-FLIM signature that was readily separated from the intrinsic fluorescence signature of tumor cells. This non-invasive quantitative technique provides a unique ability to discern specific cell types based upon their metabolic signatures without the use of exogenous fluorescent labels. Not only does this provide high resolution temporal and spatial views of macrophages in live animal breast cancer models, this approach can be extended to other animal disease models where macrophages are implicated and has potential for clinical applications.

Élastographie rénale

Renal elastography has become available with the development of noninvasive quantitative techniques (including shear-wave elastography), following the rapidly growing field of diagnosis and quantification of liver fibrosis, which has a demonstrated major clinical impact. Ultrasound or even magnetic resonance techniques are leaving the pure research area to reach the routine clinical use. With the increased incidence of chronic kidney disease and its specific morbidity and mortality, the noninvasive diagnosis of renal fibrosis can be of critical value. However, it is difficult to simply extend the application from one organ to the other due to a large number of anatomical and technical issues. Indeed, the kidney exhibits various features that make stiffness assessment more complex, such as the presence of various tissue types (cortex, medulla), high spatial orientation (anisotropy), local blood flow, fatty sinus with variable volume and echotexture, perirenal space with variable fatty content, and the variable depth of the organ. Furthermore, the stiffness changes of the renal parenchyma are not exclusively related to fibrosis, as renal perfusion or hydronephrosis will impact the local elasticity. Renal elastography might be able to diagnose acute or chronic obstruction, or to renal tumor or pseudotumor characterization. Today, renal elastography appears as a promising application that still requires optimization and validation, which is the contrary for liver stiffness assessment.

Radiotracer imaging of peripheral vascular disease.

Peripheral vascular disease (PVD) is an atherosclerotic disease affecting the lower extremities, resulting in skeletal muscle ischemia, intermittent claudication, and, in more severe stages of disease, limb amputation and death. The evaluation of therapy in this patient population can be challenging, as the standard clinical indices are insensitive to assessment of regional alterations in skeletal muscle physiology. Radiotracer imaging of the lower extremities with techniques such as PET and SPECT can provide a noninvasive quantitative technique for the evaluation of the pathophysiology associated with PVD and may complement clinical indices and other imaging approaches. This review discusses the progress in radiotracer-based evaluation of PVD and highlights recent advancements in molecular imaging with potential for clinical application.

Sodium magnetic resonance imaging of proteoglycan depletion in an in vivo model of osteoarthritis 1

Rationale and Objectives. The aim of the study was to investigate the feasibility of using sodium magnetic resonance imaging (MRI) as a noninvasive quantitative technique for measuring proteoglycan (PG) content in an in vivo porcine model of osteoarthritis (OA). Materials and Methods. Biochemical conditions similar to those of OA were created by an intra-articular injection of recombinant porcine interleukin-1β (IL-1β) into the knee joint of pigs (n = 6) before performing MRI. The contralateral knee joint was given a saline injection to serve as an internal control. Sodium MRI data were acquired on a 4-T clinical MR scanner and used to compute quantitative sodium and fixed charge density (FCD) maps based on a previously established methodology. In vivo FCD maps were compared with FCD maps obtained using ex vivo patellae harvested from the specimens. The tissue and joint fluid were subjected to histologic and immunohistochemical analyses as independent measurements of IL-1β activity and PG loss. Results. The average FCD of IL-1β-treated patellae was measured to be 49% lower than that of saline-treated patellae, indicating a loss of PG content. These results were supported by histologic and immunochemical findings, most notably a reduction in staining for PG and an increase in matrix metalloproteinases in the synovial fluid. Conclusion. Sodium MRI can serve as a quantitative method to measure in vivo changes in PG content in an animal model of OA. The use of a noninvasive quantitative in vivo PG measurement technique such as sodium MRI on an animal model would aid greatly in efforts to monitor the efficacy of treatments for OA. Furthermore, these results indicate that early degenerative events could be detected noninvasively in vivo in humans with PG-depleting diseases such as OA.

Correlation of abnormal intracranial vessel velocity, measured by transcranial Doppler ultrasonography, with abnormal conjunctival vessel velocity, measured by computer-assisted intravital microscopy, in sickle cell disease

The Stroke Prevention Trial has confirmed that utilization of transcranial Doppler ultrasonography (TCD), which examines blood flow in large intracranial vessels, can identify children with sickle cell disease (SCD) who are at high risk of developing a premature stroke. It is not known to what extent the vasculopathy in SCD involves small vessels and whether the abnormalities, if present, correlate with large-vessel vasculopathy. Eighteen children with SCD were examined with TCD to determine middle cerebral artery (MCA) velocity and computer-assisted intravital microscopy (CAIM) to determine bulbar conjunctival vessel velocity during the same visit for vasculopathy correlation. High MCA velocity (> or = 200 cm/sec) was found by TCD in 4 patients who also showed abnormal conjunctival velocity (< 0.2 mm/sec or intermittent trickle flow) by CAIM. Three patients had conditional (> or = 170 cm/sec and < 200 cm/sec) MCA velocity: 2 showed abnormal (trickle) and 1 showed normal conjunctival velocity (1.9 mm/sec). One patient with unmeasurable MCA velocity had abnormal (trickle) conjunctival velocity. Of the remaining 10 patients who had normal MCA velocity, 2 showed abnormal (0.05 mm/sec and 0.1 mm/sec) and 8 showed normal conjunctival velocities (1.1-2.4 mm/sec). The MCA velocities correlated significantly with bulbar conjunctival flow velocities (P < or =.008, Fisher exact test). A correlation exists between MCA (large-vessel) and conjunctival (small-vessel) flow velocities. CAIM is a noninvasive quantitative technique that might contribute to the identification of SCD patients at high risk of stroke. Small-vessel vasculopathy might be an important pathological indicator and should be further explored in a large-scale study. (Blood. 2001;97:3401-3404)

Familial hypophosphatemic rickets: Bone mass measurements in children following therapy with calcitriol and supplemental phosphate

Familial hypophosphatemic rickets is characterized by defective skeletal mineralization resulting in abnormal growth and development. The pathologic and radiologic correlates of this syndrome have been given some investigation, but the effect of this mineralization defect on bone mineral density has not been adequately assessed. We measured axial and appendicular bone mineral in 17 children (mean age 5.59 +/- 4.87) with familial hypophosphatemia at baseline and at 6-month intervals after initiation of therapy with vitamin D3 (calcitriol) and phosphate supplementation. Noninvasive quantitative techniques included single photon absorptiometry (SPA) of the radius, combined cortical thickness (CCT) of the second metacarpal, and quantitative computed tomography (QCT) of vertebral trabecular bone. Thoraco-lumbar and hand/wrist radiographs were qualitatively assessed for the prevalence and severity of osteosclerosis, rickets, and other parameters indicative of metabolic bone disease as well as skeletal age. Quantitative determinations of bone mineral by each technique were compared with normal values for age and sex, and individual standardized scores (z-scores) were calculated at each measurement interval. Standard scores were also calculated for bone age-adjusted mineral values. At baseline, spinal trabecular bone by QCT was not significantly different from normal values; however, measurements of peripheral cortical bone by either SPA or CCT were significantly lower than values for normal children of the same age and sex (P = 0.05 and P = 0.01, respectively). Following therapy with calcitriol and phosphate, peripheral bone mass was not shown to improve significantly when contiguous standard scores were compared even when values were adjusted for bone age.(ABSTRACT TRUNCATED AT 250 WORDS)

Tumor detection using radiolabeled monoclonal antibodies.

Radioisotope conjugated to monoclonal antibody products has been used for imaging tumors targeted by the antibody. As imaging progresses, new sets of procedural and technical questions arise. In this chapter, we discuss several current problems in imaging tumor with radiolabeled monoclonal antibody. These include (1) methods for selection of specific antibody and, once the particular antibody is selected, which fragment form is to be used; (2) imaging procedures: what are the optimum imaging parameters, such as optimum time for imaging after administration of tracer and considerations regarding background subtraction; and (3) noninvasive quantitative techniques: quantitation of localization of antibody indirectly from quantitative information in the images.