Ultrasound imaging of apoptosis: high-resolution non-invasive monitoring of programmed cell death in vitro, in situ and in vivo

A new non-invasive method for monitoring apoptosis has been developed using high frequency (40 MHz) ultrasound imaging. Conventional ultrasound backscatter imaging techniques were used to observe apoptosis occurring in response to anticancer agents in cells in vitro, in tissues ex vivo and in live animals. The mechanism behind this ultrasonic detection was identified experimentally to be the subcellular nuclear changes, condensation followed by fragmentation, that cells undergo during apoptosis. These changes dramatically increase the high frequency ultrasound scattering efficiency of apoptotic cells over normal cells (25- to 50-fold change in intensity). The result is that areas of tissue undergoing apoptosis become much brighter in comparison to surrounding viable tissues. The results provide a framework for the possibility of using high frequency ultrasound imaging in the future to non-invasively monitor the effects of chemotherapeutic agents and other anticancer treatments in experimental animal systems and in patients. © 1999 Cancer Research Campaig

Increased variability in ApcMin/+ intestinal tissue can be measured with microultrasound

Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic

High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction

<p>Abstract</p> <p>Background</p> <p>Therapeutic irreversible electroporation (IRE) is an emerging technology for the non-thermal ablation of tumors. The technique involves delivering a series of unipolar electric pulses to permanently destabilize the plasma membrane of cancer cells through an increase in transmembrane potential, which leads to the development of a tissue lesion. Clinically, IRE requires the administration of paralytic agents to prevent muscle contractions during treatment that are associated with the delivery of electric pulses. This study shows that by applying high-frequency, bipolar bursts, muscle contractions can be eliminated during IRE without compromising the non-thermal mechanism of cell death.</p> <p>Methods</p> <p>A combination of analytical, numerical, and experimental techniques were performed to investigate high-frequency irreversible electroporation (H-FIRE). A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for <it>in vivo </it>treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for <it>in vivo </it>experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation.</p> <p>Results</p> <p>No visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain.</p> <p>Conclusions</p> <p>H-FIRE is a feasible technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed with unipolar electric pulses. Therefore, it has the potential to be performed clinically without the administration of paralytic agents.</p

24-hour accelerometry in COPD: Exploring physical activity, sedentary behavior, sleep and clinical characteristics

Mark W Orme,1&ndash;3 Michael C Steiner,1&ndash;3 Mike D Morgan,1 Andrew P Kingsnorth,2,3 Dale W Esliger,2&ndash;4 Sally J Singh,1&ndash;3,* Lauren B Sherar2&ndash;4,* 1Centre for Exercise and Rehabilitation Science, NIHR Leicester Biomedical Research Centre &ndash; Respiratory, Leicester, UK; 2School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK; 3National Centre for Sport and Exercise Medicine, Loughborough, UK; 4NIHR Leicester Biomedical Research Centre, Leicester, UK *These authors contributed equally to this work Background: The constructs and interdependency of physical behaviors are not well described and the complexity of physical activity (PA) data analysis remains unexplored in COPD. This study examined the interrelationships of 24-hour physical behaviors and investigated their associations with participant characteristics for individuals with mild&ndash;moderate airflow obstruction and healthy control subjects. Patients and methods: Vigorous PA (VPA), moderate-to-vigorous PA (MVPA), light PA (LPA), stationary time (ST), average movement intensity (vector magnitude counts per minute), and sleep duration for 109 individuals with COPD and 135 healthy controls were obtained by wrist-worn accelerometry. Principal components analysis (PCA) examined interrelationships of physical behaviors to identify distinct behavioral constructs. Using the PCA component loadings, linear regressions examined associations with participant (+, positive correlation; -, negative correlation), and were compared between COPD and healthy control groups. Results: For both groups PCA revealed ST, LPA, and average movement intensity as distinct behavioral constructs to MVPA and VPA, labeled &ldquo;low-intensity movement&rdquo; and &ldquo;high-intensity movement,&rdquo; respectively. Sleep was also found to be its own distinct behavioral construct. Results from linear regressions supported the identification of distinct behavioral constructs from PCA. In COPD, low-intensity movement was associated with limitations with mobility (-), daily activities (-), health status (+), and body mass index (BMI) (-) independent of high-intensity movement and sleep. High-intensity movement was associated with age (-) and self-care limitations (-) independent of low-intensity movement and sleep. Sleep was associated with gender (0= female, 1= male; [-]), lung function (-), and percentage body fat (+) independent of low-intensity and high-intensity movement. Conclusion: Distinct behavioral constructs comprising the 24-hour day were identified as &ldquo;low-intensity movement,&rdquo; &ldquo;high-intensity movement,&rdquo; and &ldquo;sleep&rdquo; with each construct independently associated with different participant characteristics. Future research should determine whether modifying these behaviors improves health outcomes in COPD. Keywords: accelerometry, COPD, physical activity, principal components analysis, sedentary behavio

24-hour accelerometry in COPD: Exploring physical activity, sedentary behavior, sleep and clinical characteristics

Background: The constructs and interdependency of physical behaviors are not well described and the complexity of physical activity (PA) data analysis remains unexplored in COPD. This study examined the interrelationships of 24-hour physical behaviors and investigated their associations with participant characteristics for individuals with mild–moderate airflow obstruction and healthy control subjects. Patients and methods: Vigorous PA (VPA), moderate-to-vigorous PA (MVPA), light PA (LPA), stationary time (ST), average movement intensity (vector magnitude counts per minute), and sleep duration for 109 individuals with COPD and 135 healthy controls were obtained by wrist-worn accelerometry. Principal components analysis (PCA) examined interrelationships of physical behaviors to identify distinct behavioral constructs. Using the PCA component loadings, linear regressions examined associations with participant (+, positive correlation; -, negative correlation), and were compared between COPD and healthy control groups. Results: For both groups PCA revealed ST, LPA, and average movement intensity as distinct behavioral constructs to MVPA and VPA, labeled “low-intensity movement” and “high-intensity movement,” respectively. Sleep was also found to be its own distinct behavioral construct. Results from linear regressions supported the identification of distinct behavioral constructs from PCA. In COPD, low-intensity movement was associated with limitations with mobility (-), daily activities (-), health status (+), and body mass index (BMI) (-) independent of high-intensity movement and sleep. High-intensity movement was associated with age (-) and self-care limitations (-) independent of low-intensity movement and sleep. Sleep was associated with gender (0= female, 1= male; [-]), lung function (-), and percentage body fat (+) independent of low-intensity and high-intensity movement. Conclusion: Distinct behavioral constructs comprising the 24-hour day were identified as “low-intensity movement,” “high-intensity movement,” and “sleep” with each construct independently associated with different participant characteristics. Future research should determine whether modifying these behaviors improves health outcomes in COPD