ABSTRACT
To identify genetic mechanisms controlling bone marrow microcirculation and angiogenesis in patients with plasma cell disease we simultaneously performed bone marrow dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and cytogenetics (iFISH) on CD138 purified plasma cells of MGUS (n=31) and untreated multiple myeloma (MM) (n = 87) patients. The adverse cytogenetic abnormalities gain of 1q21, deletion 17p13 and deletion 13q14 significantly correlated with at least one DCE-MRI finding (aberrant "focal" microcirculation pattern, increase in median microcirculation parameter Amplitude A or exchange rate constant kep). We conclude that gain of 1q21, deletion 13q14 and deletion 17p13 trigger the angiogenic cascade in MM. Our findings will have important implications for the design, analysis and stratification for clinical studies of patients with MM in particular if compounds with antiangiogenic activity are used.
Subject(s)
Chromosome Aberrations , Chromosomes, Human, Pair 1 , Multiple Myeloma/genetics , Neovascularization, Pathologic/genetics , Female , Humans , In Situ Hybridization, Fluorescence , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Myeloma/blood supplyABSTRACT
To find a suitable method for measuring regional cerebral blood flow (rCBF) rapidly at the bedside is still a matter of investigation. The purpose here was to develop a noninvasive method for bedside rCBF measurement and to validate it with a standard method such as perfusion-weighted magnetic resonance imaging (MRI). In 11 healthy volunteers 44 measurements with near-infrared spectroscopy (NIRS) and perfusion-weighted MRI without and with a mean continuous positive airway pressure (CPAP) of 10 mbar were carried out. Four (NIRS) optodes were placed bilaterally on the forehead and 25 mg indocyanine green (ICG) was injected. New algorithms were developed to calculate rCBFNIRS and rCBVNIRS. In 6 volunteers data analysis was successful. No complications associated with the method were observed. During CPAP breathing rCBFNIRS decreased from 18.5 + 6.9 16.1 + 6.2 ml/100 g/min (P = 0.034). Mean values for rCBFMRI decreased from 256 +/- 90 to 216 +/- 62 ml/100 g/min (P = 0.012). Bland and Altman plots showed that the differences did not vary in any systematic way over the range of rCBF or rCBV values assessed and 100% of differences were within the interval mean +/- 2 SD of differences. Limits of agreement (mean +/- 2 SD) were +/- 76.4 ml/100 g/min for rCBF and +/- 15.6 ml/100 g for rCBV. The NIRS ICG dye dilution technique is a promising method for serial noninvasive bedside CBF measurements. The preliminary data indicate that measurements are in agreement with values obtained by perfusion-weighted MRI.
Subject(s)
Blood Volume/physiology , Cerebrovascular Circulation/physiology , Adult , Algorithms , Coloring Agents , Data Interpretation, Statistical , Dye Dilution Technique , Female , Functional Laterality/physiology , Humans , Indocyanine Green , Magnetic Resonance Imaging , Male , Positive-Pressure Respiration , Reproducibility of Results , Spectroscopy, Near-InfraredABSTRACT
Indocyanine green (ICG) has excellent safety records and is widely used in medical diagnosis. Recently, a new method has been developed to estimate cerebral blood flow (CBF) using ICG in combination with near-infrared spectroscopy (NIRS). The new technique may be of wide clinical interest, as it is noninvasive and easy to perform at the bedside in stroke patients. Additionally, ICG with the use of specific wavelength lasers is documented to be effective in photodynamic therapy (PDT). Under normal conditions ICG does not cross the intact blood brain barrier (BBB). However, in patients with brain injuries where the BBB may be disturbed, ICG could accumulate in brain parenchyma and in combination with NIR-light exposure, phototoxicity could occur. The aim of the present study was to examine the possible toxicity of ICG in combination with NIRS in a specific setting for CBF measurements. In five rats with mannitol induced BBB breakdown no traces of ICG were found during spectrophotometric analysis of the brain cell suspensions. In ten rats with disrupted BBB there were no significant increases of brain temperature or histological signs of brain damage following 1 h NIR-light exposure after ICG injection. The existing literature concerning the application of ICG in combination with NIR light is reviewed.
