Thresholds For Tissue Damage Research Articles

Computation of ultrasonic pressure fields in feline brain

In 1975, Dunn et al. (JASA 58, 512–514) showed that a simple relation describes the ultrasonic threshold for cavitation-induced changes in the mammalian brain. The thresholds for tissue damage were estimated for a variety of acoustic parameters in exposed feline brain. The goal of this study was to improve the estimates for acoustic pressures and intensities present in vivo during experimental exposures rather than estimating them using linear theory. In our current project, the acoustic pressure waveforms produced in the brains of anesthetized felines were numerically simulated for a spherically focused, nominally f1-transducer (focal length = 13 cm) at increasing values of the source pressure at frequencies of 1, 3, and 9 MHz. The corresponding focal intensities were correlated with the experimental data of Dunn et al. The focal pressure waveforms were also computed at the location of the true maximum. For low source pressures, the computed waveforms were the same as those determined using linear theory...

Scleral cross-linking by riboflavin and blue light application in young rabbits: damage threshold and eye growth inhibition.

Scleral cross-linking (SXL) by riboflavin and light application has been introduced as a possible treatment to increase scleral tissue stiffness and to inhibit excessive axial elongation of highly myopic eyes. We evaluated an ocular tissue damage threshold for blue light irradiation, and used SXL treatment to induce eye growth inhibition. The sclera of 3-week-old rabbits (39 pigmented and 15 albino rabbits) were treated with different blue light intensities (450 ± 50 nm) and riboflavin. Alterations and a damage threshold were detected in ocular tissues by means of light microscopy and immunohistochemistry. The influence of SXL on the eye growth was examined in 21 young rabbits and was measured by using A-scan ultrasonography, micrometer caliper, and for selected eyes additionally by MR imaging. Light microscopic examinations demonstrated degenerative changes in ocular tissue after irradiation with blue light intensities above 400 mW/cm(2) (with and without riboflavin application). Therefore, that light intensity was defined as the damage threshold. Tissue alteration in retina, choroid, and sclera and activation of retinal microglia cells and Müller cells could be earlier observed at blue light intensities of 150 and 200 mW/cm(2). Albino rabbits were less sensitive to this SXL treatment. A significant reduction of the eye growth could be detected by SXL treatment with the minimal efficient blue light intensity of 15 mW/cm(2) and maintained stable for 24 weeks. SXL with riboflavin and blue light intensities below a defined damage threshold can induce a long lasting growth inhibitory effect on young rabbit eyes. Therefore, SXL might be a realistic approach to inhibit eye elongation in highly myopic eyes.

Thermal effects of λ = 808 nm GaAlAs diode laser irradiation on different titanium surfaces.

Diode lasers are widely used in dental laser treatment, but little is known about their thermal effects on different titanium implant surfaces. This is a key issue because already a 10 °C increase over the normal body temperature can induce bone injury and compromise osseo-integration. The present study aimed at evaluating the temperature changes and surface alterations experienced by different titanium surfaces upon irradiation with a λ = 808 nm diode laser with different settings and modalities. Titanium discs with surfaces mimicking different dental implant surfaces including TiUnite and anodized, machined surfaces were laser-irradiated in contact and non-contact mode, and with and without airflow cooling. Settings were 0.5-2.0 W for the continuous wave mode and 10-45 μJ, 20 kHz, 5-20 μs for the pulsed wave mode. The results show that the surface characteristics have a marked influence on temperature changes in response to irradiation. The TiUnite surface, corresponding to the osseous interface of dental implants, was the most susceptible to thermal rise, while the machined surfaces, corresponding to the implant collar, were less affected. In non-contact mode and upon continuous wave emission, the temperature rose above the 50 °C tissue damage threshold. Scanning electron microscopy investigation of surface alterations revealed that laser treatment in contact mode resulted in surface scratches even when no irradiation was performed. These findings indicate that the effects of diode laser irradiation on implant surfaces depend on physical features of the titanium coating and that in order to avoid thermal or physical damage to implant surface the irradiation treatment has to be carefully selected.

Experimental investigation and histopathological identification of acute thermal damage in skeletal porcine muscle in relation to whole-body SAR, maximum temperature, and CEM43 °C due to RF irradiation in an MR body coil of birdcage type at 123 MHz

Purpose: This study is an investigation of the relationship between several characteristic parameters and acute thermal damage in porcine skeletal muscle. Material and methods: Fourteen pigs under injection anaesthesia were placed into a magnetic resonance body coil and exposed for different time durations to different specific energy absorption rate (SAR) levels at 123 MHz. Local temperatures were measured using four temperature sensors. Sensors 1–3 were placed in skeletal muscle and one sensor was placed in the rectum. Sensors 1 and 2 were placed in hot-spot areas and sensor 3 was placed at the periphery of the animals. The pigs were exposed to whole-body SAR (SAR-wb) between 2.5 W/kg and 5.2 W/kg for 30 or 60 min. Three animals received no SAR. After each experiment, muscle samples adjacent to the positions of sensors 1–3 were taken for frozen section analysis. Three characteristic parameters were chosen for investigation: SAR-wb, maximum sensor temperature (T-max), and cumulative equivalent minutes at 43 °C (CEM43 °C). Results: Histopathological criteria were established to detect acute thermal tissue damage in frozen sections such as widening of intercellular space between the muscle fibres and loss of glycogen. Clear tissue damage thresholds were found for T-max and CEM43 °C, though not for SAR-wb. For all animals with high thermal exposure, damage was also found for muscle samples adjacent to the peripheral sensor 3. Conclusions: Both T-max and CEM43, are able to predict thermal damage in porcine muscle. However, CEM43 is the less ambiguous parameter. The reasons for the occurrence of the aforementioned damage at low local temperatures at the animals’ periphery remain unclear and further investigations are needed.

Scleral crosslinking as a therapeutic approach to treat progressive myopia

AbstractIntroduction Elongation of the bulbus is the main cause of high myopia. Light induced scleral crosslinking is suggested as a therapeutic approach to prevent extensive eye elongation . Data about efficient light intensities and light‐induced damage threshold of retinal tissue are not conclusive. There are no data available about the effect on eye growth of light induced crosslinking in an animal model. Material an methods In vitro and in vivo experiments in rabbits were performed with riboflavin/blue light application for scleral crosslinking. Mechanical stiffening effects were studied by means of rheology and tissue damage threshold were characterized by histology and electron microscopy. Results Collagen Crosslinking by riboflavin/blue light stiffens the scleral tissue and induced a significant reduction of eye growth in young rabbits without damaging effects on retinal tissue. Conclusion Riboflavin/Blue light treatment might be a promissing treatment to control eye growth and therefore, to prevent high myopia. More investigations are needed to establish optimal treatment parameters. Commercial interest

What Are the Current Clinical Issues in Wear and Tribocorrosion?

Wear and corrosion in joint arthroplasty are important causes of failure. From the standpoint of current clinical importance, there are four main categories of wear and tribocorrosion: polyethylene wear, ceramic-on-ceramic (CoC) bearing wear, metal-on-metal (MoM) bearing wear, and taper tribocorrosion. Recently, problems with wear in the knee have become less prominent as have many issues with hip polyethylene (PE) bearings resulting from the success of crosslinked PE. However, MoM articulations and taper tribocorrosion have been associated with soft tissue inflammatory responses, and as a result, they have become prominent clinical concerns. WHERE ARE WE NOW?: For PE wear in the hip, several advances include improved locking mechanisms and data supporting highly crosslinked polyethylenes (HXLPE). Edge-loading in CoC articulations can contribute to stripe wear and subsequent squeaking. For MoM articulations, the relationship of wear-to-edge loading, sensitivity to component positioning, typical soft tissue response, and use of imaging is increasingly understood. Taper tribocorrosion (from femoral head-neck junctions and other modular elements) and associated soft tissue inflammatory responses appear to be serious clinical issues that are not fully understood. WHERE DO WE NEED TO GO?: In the knee, clinical concerns remain with the efficacy of HXLPE, modular connections, and metal allergies. For PE wear in the hip, concerns remain regarding how to increase crosslinking of PE while minimizing PE fractures. With CoC articulations, questions remain on how to prevent noises, chipping, and impingement and if enhanced designs can contribute to improved results. For MoM articulations, we need to improve imaging tests for soft tissue reactions, determine best practices in terms of monitoring protocols, and better define if, how, and when to act on serum metal levels. For taper tribocorrosion, we need to use modularity wisely and also understand how to improve tapers and materials in the future. For patients at risk for tribocorrosion, we need to define realistic diagnostic and monitoring protocols. We also need to enhance revision methods, and the threshold of acceptable soft tissue damage, to minimize complications associated with soft tissue damage such as hip instability. HOW DO WE GET THERE?: HXLPE and other bearing surfaces will likely continue to be refined. We need to develop tapers with more resistance to tribocorrosion through improved understanding of the manufacturing process and ongoing engineering improvements. Revision procedures for wear and tribocorrosion can be enhanced by determining when partial component retention is appropriate and how best to manage soft tissue damage. For CoC articulations, enhanced designs are required to minimize noises, chipping, and impingement. Importantly, we must continue to promote and analyze joint replacement registries to identify early failures and analyze long-term successes.

Methods for reducing peak pressure in laparoscopic grasping

During tissue retraction with a laparoscopic grasper, tissue-damaging pressures can occur. Past research suggests that peak pressures can be considerably reduced by rounding the edges or covering the tip of the end effector with a silicon sleeve. To identify grasping methods that limit tissue damage, the effects of (a) Young's modulus of the end effector, (b) curvature of the end effector, and (c) angle with which the tissue is pulled relative to the plane of the end effector, on the pressure generated on the tissue were investigated. Artificial skin was placed between two non-serrated jaws, a pressure-sensitive film was interposed between the skin and upper jaw, and the end effector was loaded with 13 N. End effectors with Young's moduli of 0.09, 0.67, 1.49 MPa, and 69 GPa, and with non-rounded and 5 mm rounded edges were tested under pulling angles of 25°, 50°, and 75°. For non-rounded end effectors, the maximum pressure and the area across which pressure exceeded the safety threshold for tissue damage increased with Young's modulus and pulling angle. For rounded end effectors, maximum pressure did not increase monotonically with Young's modulus. Instead, the end effector with the second lowest Young's modulus yielded significantly lower maximum pressure than the end effector with the lowest Young's modulus. For rounded end effectors, pressures were below the safety threshold for all Young's moduli. This indicates that to prevent tissue damage, soft graspers may not be needed; rounding the edges of metal graspers could suffice for preventing tissue damage.

Non-invasive ultrasonic surgery of the brain in non-human primates

High-intensity focused ultrasound causes selective tissue necrosis efficiently and safely, namely, in the prostate, liver, and uterine fibroid. Nevertheless, ablation of brain tissue using focused ultrasound remains limited due to strong aberrations induced by the skull. To achieve ultrasonic transcranial brain ablation, such aberrations have to be compensated. In this study, non-invasive therapy was performed on monkeys using adaptive correction of the therapeutic beam and 3D simulations of transcranial wave propagation based on 3D computed tomographic (CT) scan information. The aim of the study was two-fold: induce lesions in a non-human primate brain non-invasively and investigate the potential side effects. Stereotactic targeting was performed on five Macaca fascicularis individuals. Each hemisphere was treated separately with a 15-day interval and animals were sacrificed two days after the last treatment. The ultrasonic dose delivered at the focus was increased from one treatment location to the other to estimate the thermal dose for tissue alteration. Thermal doses in the brain were determined by numerical computations. Treatment efficiency and safety were evaluated histologically. The threshold for tissue damage in the brain was measured to be between 90 and 280 cumulative equivalent minutes at 43 °C. Intravenous injection of corticoids before the treatment limited the side effects.

Thresholds for thermal damage to normal tissues: An update

The purpose of this review is to summarise a literature survey on thermal thresholds for tissue damage. This review covers published literature for the consecutive years from 2002–2009. The first review on this subject was published in 2003. It included an extensive discussion of how to use thermal dosimetric principles to normalise all time-temperature data histories to a common format. This review utilises those same principles to address sensitivity of a variety of tissues, but with particular emphasis on brain and testis. The review includes new data on tissues that were not included in the original review. Several important observations have come from this review. First, a large proportion of the papers examined for this review were discarded because time–temperature history at the site of thermal damage assessment was not recorded. It is strongly recommended that future research on this subject include such data. Second, very little data is available examining chronic consequences of thermal exposure. On a related point, the time of assessment of damage after exposure is critically important for assessing whether damage is transient or permanent. Additionally, virtually no data are available for repeated thermal exposures which may occur in certain recreational or occupational activities. For purposes of regulatory guidelines, both acute and lasting effects of thermal damage should be considered.

A Comparison of the Thermal-Dose Equation and the Intensity-Time Product, Itm, for Predicting Tissue Damage Thresholds

Thermal dose is the most generally accepted concept for estimating temperature-related tissue damage thresholds in high-intensity focused ultrasound (HIFU) procedures. However, another approach based on the intensity-time product I t m = D has been used, where D is a tissue-dependent damage threshold, I is the spatial-peak, temporal-average intensity and t is time. In this study, these two approaches were compared analytically by substituting a well-known soft-tissue solution for temperature vs. time into the thermal dose equation. From power law fits of I vs. t, m was found to fall between about 0.3 and 0.8. In terms of the intensity required for cell death for a given exposure time, the standard deviation of the error between the full thermal-dose formulation and the I t m = D prediction based upon the power-law fit was less than 5% for focal beam diameters up to 3 mm. Thus, for the practical range of HIFU parameters examined, the intensity-time product relationship is equivalent to the thermal dose formulation. (E-mail: gerald.harris@fda.hhs.gov)

The importance of internal strain as opposed to interface pressure in the prevention of pressure related deep tissue injury

For pressure ulcer prevention an ambitious goal would be the establishment of a mechanical threshold for tissue damage. In the past, several researchers have sought to establish such a threshold often involving the loading time. However, they have not resulted in a unique reliable value that could be used in practice. This limitation is probably due to the focus on interface pressure. The objective of this paper is to clarify to an audience with no conventional background in mechanics, why interface pressure is not the appropriate parameter to define a damage threshold, whereas internal local deformations (strains) may prove more suitable. The paper reveals that it may be possible to identify a damage threshold for healthy skeletal muscle tissue based on local internal deformations.

A Targeting Method Based on Acoustic Backscatter for Treatment Planning in Tissue Ablation Using Focused Ultrasound

High-intensity focused ultrasound (HIFU) is a therapeutic modality that can produce coagulative necrosis in biological tissue, noninvasively. This technique requires the determination of the focus of a HIFU transducer before treatment. We investigated a method to localize the focus based on the change in radio-frequency (RF) signal at HIFU intensity levels below the threshold for tissue damage. 2-D RF data were collected during the HIFU exposure at subablative intensity levels in ex vivo chicken tissue. The HIFU intensity was then increased to induce necrotic lesions in tissue, visualized as hyperecho in B-mode images, and the location of hyperecho was used to represent physical lesions, as established in our prior studies. Results showed that focal RF amplitude increased immediately after HIFU started at subablative intensity. The focus was clearly visualized in a 2-D map of the average rate of change (ARC) of RF amplitude. The 2-D difference between focus locations based on RF data and hyperecho was 1.92 +/- 1.02 mm (mean +/- standard deviation), with no statistically significant difference (axial: p = 0.50, lateral: p = 0.07, paired t -test). Histological analysis was also performed to examine structural change in tissue after HIFU exposure. The results indicated that ARC map could be used to determine the focus of a HIFU transducer at subablative intensity, and it has the potential to be used for HIFU treatment targeting.

Fluorescence diffuse optical tomography using upconverting nanoparticles

Fluorescence diffuse optical tomography (FDOT) can provide important information in biomedical studies. In this ill-posed problem, suppression of background tissue autofluorescence is of utmost importance. We report a method for autofluorescence-insensitive FDOT using nonlinear upconverting nanoparticles (NaYF4:Yb3+/Tm3+) in a tissue phantom under excitation intensities well below tissue-damage thresholds. Even with the intrinsic autofluorescence from the phantom only, the reconstruction of the nanoparticles is of much better quality than the reconstruction of a Stokes-shifting dye. In addition, the nonlinear power dependence leads to more confined reconstructions and may increase the resolution in FDOT.

Establishing safety limits for transcranial direct current stimulation

Establishing safety limits for transcranial direct current stimulation

The Risk of Exposure to Diagnostic Ultrasound in Postnatal Subjects

This review evaluates the thermal mechanism for ultrasound-induced biological effects in postnatal subjects. The focus is the evaluation of damage versus temperature increase. A view of ultrasound-induced temperature increase is presented, based on thermodynamic Arrhenius analyses. The hyperthermia and other literature revealed data that allowed for an estimate of a temperature increase threshold of tissue damage for very short exposure times. This evaluation yielded an exposure time extension of the 1997 American Institute of Ultrasound in Medicine Conclusions Regarding Heat statement (American Institute of Ultrasound in Medicine, Laurel, MD) to 0.1 second for nonfetal tissue, where, at this exposure time, the temperature increase threshold of tissue damage was estimated to be about 18 degrees C. The output display standard was also evaluated for soft tissue and bone cases, and it was concluded that the current thermal indices could be improved to reduce the deviations and scatter of computed maximum temperature rises.

Ischemic Preconditioning: Postischemic Structural Changes in the Brain

Ischemic brain damage can be prevented or at least significantly reduced when there is a preceding brief ischemic period that does not exceed the threshold for tissue damage--a phenomenon termed "ischemic preconditioning" (ischemic PC). Experimental PC in rodents is now considered to be a model for transient ischemic attacks in humans, and there is increasing hope for translating the knowledge of underlying mechanisms in the animal models into the clinic to enhance endogenous neuroprotective mechanisms in patients with stroke. However, although PC was originally defined as a subtoxic stimulus without any morphologic damage, there is a growing body of evidence from studies using sensitive techniques that postischemic structural alterations of brain tissue manifest not only after ischemia with prior PC but also after the PC stimulus itself. Furthermore, it has become evident over time that the primary shortcomings of many experimental studies on PC are the short observation intervals. The few studies with extended postischemic survival periods done to date provide clear evidence of considerable structural changes and even cell death, which may only be postponed by PC. Therefore, further studies are needed to elucidate structural long-term changes after PC and to validate the persistence of the neuroprotective effects.

Plasma needle for in vivo medical treatment: recent developments and perspectives

In this paper we describe the hitherto unravelled facts on the interactions of a cold atmospheric plasma with living cells and tissues. A specially designed source, plasma needle, is a low-power discharge, which operates under the threshold of tissue damage. When applied properly, the needle does not cause fatal cell injury which would result in cell death (necrosis). Instead, it allows precise and localized cell removal by means of the so-called cell detachment. In addition, plasma can be used for bacterial disinfection. Because of mild treatment conditions, plasma disinfection can be performed in vivo, e.g. on wounds and dental cavities. Presently, one strives to obtain a better control of the operating device. Therefore, plasma has been characterized using a variety of diagnostics, and a smart system has been designed for the positioning of the device with respect to the treated surface.

Effects of contrast agent infusion rates on thresholds for tissue damage produced by single exposures of high-intensity ultrasound

Stabilized microbubble ultrasound contrast agents (UCA) have potential to aid tissue ablation during ultrasound surgery by enhancing both cavitational and thermal damage mechanisms. Previously, we showed UCA infused at a rate of 1 microL/kg/min prior to ultrasound exposure could reduce the total energy required to produce tissue damage by up to two orders of magnitude. In this paper, we evaluate thresholds for macroscopic tissue damage with UCA infusion rates (IR) of 0.1, 0.3, 1, 3, and 10 microL/kg/min to determine IR potentially effective for ultrasound therapy. Canine kidneys were surgically externalized and insonified with single exposures of focused ultrasound. Incident exposures were 1.44 MHz tone bursts, either 250 ms in duration with intensity between 500 W/cm2 and 3200 W/cm2, or 100 micros to 1 s in duration with intensity equal to 3200 W/cm2. Probabilities of tissue damage occurrence were determined for each set of exposure conditions (intensity, duration, and IR). A threshold intensity and threshold duration, defined as the quantities for which tissue damage occurred with probability equal to 0.5, were estimated for each IR. Results show that, as IR increased from 0.1 to 10 microL/kg/min, the threshold intensity decreased by up to a factor of 3, and threshold duration decreased by up to a factor of 200. Microbubble introduction at IR up to 10 microL/kg/min thus may be effective in aiding ultrasound therapy.

Physiological thresholds for irreversible tissue damage in contusional regions following traumatic brain injury

Cerebral ischaemia appears to be an important mechanism of secondary neuronal injury in traumatic brain injury (TBI) and is an important predictor of outcome. To date, the thresholds of cerebral blood flow (CBF) and cerebral oxygen utilization (CMRO(2)) for irreversible tissue damage used in TBI studies have been adopted from experimental and clinical ischaemic stroke studies. Identification of irreversibly damaged tissue in the acute phase following TBI could have considerable therapeutic and prognostic implications. However, it is questionable whether stroke thresholds are applicable to TBI. Therefore, the aim of this study was to determine physiological thresholds for the development of irreversible tissue damage in contusional and pericontusional regions in TBI, and to determine the ability of such thresholds to accurately differentiate irreversibly damaged tissue. This study involved 14 patients with structural abnormalities on late-stage MRI, all of whom had been studied with (15)O PET within 72 h of TBI. Lesion regions of interest (ROI) and non-lesion ROIs were constructed on late-stage MRIs and applied to co-registered PET maps of CBF, CMRO(2) and oxygen extraction fraction (OEF). From the entire population of voxels in non-lesion ROIs, we determined thresholds for the development of irreversible tissue damage as the lower limit of the 95% confidence interval for CBF, CMRO(2) and OEF. To test the ability of a physiological variable to differentiate lesion and non-lesion tissue, we constructed probability curves, demonstrating the ability of a physiological variable to predict lesion and non-lesion outcomes. The lower limits of the 95% confidence interval for CBF, CMRO(2) and OEF in non-lesion tissue were 15.0 ml/100 ml/min, 36.7 mumol/100 ml/min and 25.9% respectively. Voxels below these values were significantly more frequent in lesion tissue (all P < 0.005, Mann-Whitney U-test). However, a significant proportion of lesion voxels had values above these thresholds, so that definition of the full extent of irreversible tissue damage would not be possible based upon single physiological thresholds. We conclude that, in TBI, the threshold of CBF below which irreversible tissue damage consistently occurs differs from the classical CBF threshold for stroke (where similar methodology is used to define such thresholds). The CMRO(2) threshold is comparable to that reported in the stroke literature. At a voxel-based level, however (and in common with ischaemic stroke), the extent of irreversible tissue damage cannot be accurately predicted by early abnormalities of any single physiological variable.

Update on stroke

This review highlights the progress achieved in stroke during the last year, and emphasizes recent controversies concerning its pathophysiology, therapy and secondary complications. Studies published in 2004 provided new insights into the therapeutic window and ischemic penumbra, thrombolysis therapy, uncommon risk factors for stroke, and neuropsychological post-stroke complications. Despite the diffusion-perfusion mismatch remaining the most widely used technique to identify thresholds for ischemic penumbra and irreversible brain tissue damage, new imaging such as arterial spin-labeling perfusion and computed tomographic perfusion may define this impaired tissue more accurately. New studies assessed the relation of the interval from stroke onset to start intravenous thrombolysis treatment (tissue plasminogen activator) on favorable 3-month outcome, and on the occurrence of clinically relevant parenchymal hemorrhage: the benefit of tissue plasminogen activator could extend beyond 3 h, but with a few risks. Systemic inflammations and infections have been found to be associated with a substantial increase in the risk of developing vascular events, supporting the concept that systemic inflammation itself alters the probability of stroke occurrence. Recent literature concerning neuropsychological post-stroke complications focused mainly on the concept of mixed dementia and confirmed that mood disorders are common after stroke, and interfere with its long-term outcome. Significant advances have been made during the last year in determining more accurately the therapeutic window, using new strategies and clinical markers. Moreover, new light has been thrown on less common stroke risk factors, and neuropsychological post-stroke complications.