Computed Ultrasound Tomography in Echo mode (CUTE) of speed of sound for diagnosis and for aberration correction in pulse-echo sonography

Sound speed as a diagnostic marker for various diseases of human tissue has been of interest for a while. Up to now, mostly transmission ultrasound computed tomography (UCT) was able to detect spatially resolved sound speed, and its promise as a diagnostic tool has been demonstrated. However, UCT is limited to acoustically transparent samples such as the breast. We present a novel technique where spatially resolved detection of sound speed can be achieved using conventional pulse-echo equipment in reflection mode. For this purpose, pulse-echo images are acquired under various transmit beam directions and a two-dimensional map of the sound speed is reconstructed from the changing phase of local echoes using a direct reconstruction method. Phantom results demonstrate that a high spatial resolution (1 mm) and contrast (0.5 % of average sound speed) can be achieved suitable for diagnostic purposes. In comparison to previous reflection-mode based methods, CUTE works also in a situation with only diffuse echoes, and its direct reconstruction algorithm enables real-time application. This makes it suitable as an addition to conventional clinical ultrasound where it has the potential to benefit diagnosis in a multimodal approach. In addition, knowledge of the spatial distribution of sound speed allows full aberration correction and thus improved spatial resolution and contrast of conventional B-mode ultrasound. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

In-vivo phase contrast magnetic resonance angiography of the cerebrovascular system: a comparative study with duplex sonography.

PURPOSE Assessment of the cerebral blood flow (CBF) is crucial in the evaluation of patients with steno-occlusive diseases of the arteries supplying the brain for prediction of stroke risk. Quantitative phase contrast magnetic resonance angiography (PC-MRA) can be utilised for noninvasive quantification of CBF. The aim of this study was to validate in-vivo PC-MRA data by comparing them with colour-coded duplex (CCD) sonography in patients with cerebrovascular disease. METHODS AND MATERIALS We examined 24 consecutive patients (mean age 63 years) with stenosis of arteries supplying the brain using PC-MRA and CCD. Velocities were measured in a total of 209 stenotic and healthy arterial segments (110 extra- and 99 intracranial). RESULTS Moderate to good correlation of velocity measurements between both techniques was observed in all six extracranial and five out of seven intracranial segments (p <0.05). Velocities measured with CCD sonography were generally higher than those obtained by PC-MRA. Reversal of flow direction was detected consistently with both methods. CONCLUSION PC-MRA represents a robust, standardised magnetic resonance imaging technique for blood flow measurements within a reasonable acquisition time, potentially evolving as valuable work-up tool for more precise patient stratification for revascularisation therapy. PC-MRA overcomes relevant weaknesses of CCD in being not operator-dependent and not relying on a bone window to assess the intracranial arteries.

Computed Ultrasound Tomography in Echo Mode for Imaging Speed of Sound Using Pulse-Echo Sonography: Proof of Principle

The limitations of diagnostic echo ultrasound have motivated research into novel modalities that complement ultrasound in a multimodal device. One promising candidate is speed of sound imaging, which has been found to reveal structural changes in diseased tissue. Transmission ultrasound tomography shows speed of sound spatially resolved, but is limited to the acoustically transparent breast. We present a novel method by which speed-of-sound imaging is possible using classic pulse-echo equipment, facilitating new clinical applications and the combination with state-of-the art diagnostic ultrasound. Pulse-echo images are reconstructed while scanning the tissue under various angles using transmit beam steering. Differences in average sound speed along different transmit directions are reflected in the local echo phase, which allows a 2-D reconstruction of the sound speed. In the present proof-of-principle study, we describe a contrast resolution of 0.6% of average sound speed and a spatial resolution of 1 mm (laterally) × 3 mm (axially), suitable for diagnostic applications.

The acute adaptations of normal and pathological human Achilles tendons to eccentric and concentric exercise

Eccentric exercise is the conservative treatment of choice for mid-portion Achilles tendinopathy. While there is a growing body of evidence supporting the medium to long term efficacy of eccentric exercise in Achilles tendinopathy treatment, very few studies have investigated the short term response of the tendon to eccentric exercise. Moreover, the mechanisms through which tendinopathy symptom resolution occurs remain to be established. The primary purpose of this thesis was to investigate the acute adaptations of the Achilles tendon to, and the biomechanical characteristics of, the eccentric exercise protocol used for Achilles tendinopathy rehabilitation and a concentric equivalent. The research was conducted with an orientation towards exploring potential mechanisms through which eccentric exercise may bring about a resolution of tendinopathy symptoms. Specifically, the morphology of tendinopathic and normal Achilles tendons was monitored using high resolution sonography prior to and following eccentric and concentric exercise, to facilitate comparison between the treatment of choice and a similar alternative. To date, the only proposed mechanism through which eccentric exercise is thought to result in symptom resolution is the increased variability in motor output force observed during eccentric exercise. This thesis expanded upon prior work by investigating the variability in motor output force recorded during eccentric and concentric exercises, when performed at two different knee joint angles, by limbs with and without symptomatic tendinopathy. The methodological phase of the research focused on establishing the reliability of measures of tendon thickness, tendon echogenicity, electromyography (EMG) of the Triceps Surae and the standard deviation (SD) and power spectral density (PSD) of the vertical ground reaction force (VGRF). These analyses facilitated comparison between the error in the measurements and experimental differences identified as statistically significant, so that the importance and meaning of the experimental differences could be established. One potential limitation of monitoring the morphological response of the Achilles tendon to exercise loading is that the Achilles tendon is continually exposed to additional loading as participants complete the walking required to carry out their necessary daily tasks. The specific purpose of the last experiment in the methodological phase was to evaluate the effect of incidental walking activity on Achilles tendon morphology. The results of this study indicated that walking activity could decrease Achilles tendon thickness (negative diametral strain) and that the decrease in thickness was dependent on both the amount of walking completed and the proximity of walking activity to the sonographic examination. Thus, incidental walking activity was identified as a potentially confounding factor for future experiments which endeavoured to monitor changes in tendon thickness with exercise loading. In the experimental phase of this thesis the thickness of Achilles tendons was monitored prior to and following isolated eccentric and concentric exercise. The initial pilot study demonstrated that eccentric exercise resulted in a greater acute decrease in Achilles tendon thickness (greater diametral strain) compared to an equivalent concentric exercise, in participants with no history of Achilles tendon pain. This experiment was then expanded to incorporate participants with unilateral Achilles tendinopathy. The major finding of this experiment was that the acute decrease in Achilles tendon thickness observed following eccentric exercise was modified by the presence of tendinopathy, with a smaller decrease (less diametral strain) noted for tendinopathic compared to healthy control tendon. Based on in vitro evidence a decrease in tendon thickness is believed to reflect extrusion of fluid from the tendon with loading. This process would appear to be limited by the presence of pathology and is hypothesised to be a result of the changes in tendon structure associated with tendinopathy. Load induced fluid movement may be important to the maintenance of tendon homeostasis and structure as it has the potential to enhance molecular movement and stimulate tendon remodelling. On this basis eccentric exercise may be more beneficial to the tendon than concentric exercise. Finally, EMG and motor output force variability (SD and PSD of VGRF) were investigated while participants with and without tendinopathy performed the eccentric and concentric exercises. Although between condition differences were identified as statistically significant for a number of force variability parameters, the differences were not greater than the limits of agreement for repeated measures. Consequently the meaning and importance of these findings were questioned. Interestingly, the EMG amplitude of all three Triceps Surae muscles did not vary with knee joint angle during the performance of eccentric exercise. This raises questions pertaining to the functional importance of performing the eccentric exercise protocol at each of the two knee joint angles as it is currently prescribed. EMG amplitude was significantly greater during concentric compared to eccentric muscle actions. Differences in the muscle activation patterns may result in different stress distributions within the tendon and be related to the different diametral strain responses observed for eccentric and concentric muscle actions.

Achilles tendinopathy has an aberrant strain response to eccentric exercise

Purpose: Eccentric exercise has become the treatment of choice for Achilles tendinopathy. However, little is known about the acute response of tendons to eccentric exercise or the mechanisms underlying its clinical benefit. This research evaluated the sonographic characteristics and acute anteroposterior (AP) strain response of control (healthy), asymptomatic, and symptomatic Achilles tendons to eccentric exercise. Methods: Eleven male adults with unilateral midportion Achilles tendinopathy and nine control male adults without tendinopathy participated in the research. Sagittal sonograms of the Achilles tendon were acquired immediately before and after completion of a common eccentric rehabilitation exercise protocol and again 24 h later. Tendon thickness, echogenicity, and AP strain were determined 40 mm proximal to the calcaneal insertion. Results: Compared with the control tendon, both the asymptomatic and symptomatic tendons were thicker (P < 0.05) and hypoechoic (P < 0.05) at baseline. All tendons decreased in thickness immediately after eccentric exercise (P < 0.05). The symptomatic tendon was characterized by a significantly lower AP strain response to eccentric exercise compared with both the asymptomatic and control tendons (P < 0.05). AP strains did not differ in the control and asymptomatic tendons. For all tendons, preexercise thickness was restored 24 h after exercise completion. Conclusions: These observations support the concept that Achilles tendinopathy is a bilateral or systemic process and structural changes associated with symptomatic tendinopathy alter fluid movement within the tendon matrix. Altered fluid movement may disrupt remodeling and homeostatic processes and represents a plausible mechanism underlying the progression of tendinopathy.

Load bearing improves the limits of agreement for repeated in vivo measures of the speed of sound in human Achilles tendon

Axial acoustic wave propagation has been widely used in evaluating the mechanical properties of human bone in vivo. However, application of this technique to monitor soft tissues, such as tendon, has received comparatively little scientific attention. Laboratory-based research has established that axial acoustic wave transmission is not only related to the physical properties of equine tendon but is also proportional to tensile load to which it is exposed (Miles et al., 1996; Pourcelot et al., 2005). The reproducibility of the technique for in vivo measurements in human tendon, however, has not been established. The aim of this study was to evaluate the limits of agreement for repeated measures of the speed of sound (SoS) in human Achilles tendon in vivo. Methods: A custom built ultrasound device, consisting of an A-mode 1MHz emitter and two regularly spaced receivers, was used to measure the SoS in the mid-portion of the Achilles tendon in ten healthy males and ten females (mean age: 33.8 years, range 23-56 yrs; height: 1.73±0.08 m; weight: 68.4±15.3 kg). The emitter and receivers were held at fixed positions by a polyethylene frame and maintained in close contact with the skin overlying the tendon by means of elasticated straps. Repeated SoS measurements were taken with the subject prone (non-weightbearing and relaxed Achilles tendon) and during quiet bipedal and unipedal stance. In each instance, the device was detached and repositioned prior to measurement. Results: Limits of agreement for repeated SoS measures during non-weightbearing and bipedal and unipedal stance were ±53, ±28 and ±21 m/s, respectively. The average SoS in the non-weightbearing Achilles tendon was 1804±198 m/s. There was a significant increase in the average SoS during bilateral (2122±135 m/s) (P < 0.05) and unilateral (2221±79 m/s) stance (P < 0.05). Conclusions: Repeated SoS measures in human Achilles tendon were more reliable during stance than under non-weightbearing conditions. These findings are consistent with previous research in equine tendon in which lower variability in SoS was observed with increasing tensile load (Crevier-Denoix et al, 2009). Since the limits of agreement for Achilles tendon SoS are nearly 5% of the changes previously observed during walking and therapeutic heel raise exercises, acoustic wave transmission provides a promising new non-invasive method for determining tendon properties during sports and rehabilitation related activities.

Prediction of maximal surface electromyographically based voluntary contractions of erector spinae muscles from sonographic measurements during isometric contractions

Objectives Currently, there are no studies combining electromyography (EMG) and sonography to estimate the absolute and relative strength values of erector spinae (ES) muscles in healthy individuals. The purpose of this study was to establish whether the maximum voluntary contraction (MVC) of the ES during isometric contractions could be predicted from the changes in surface EMG as well as in fiber pennation and thickness as measured by sonography. Methods Thirty healthy adults performed 3 isometric extensions at 45° from the vertical to calculate the MVC force. Contractions at 33% and 100% of the MVC force were then used during sonographic and EMG recordings. These measurements were used to observe the architecture and function of the muscles during contraction. Statistical analysis was performed using bivariate regression and regression equations. Results The slope for each regression equation was statistically significant (P < .001) with R2 values of 0.837 and 0.986 for the right and left ES, respectively. The standard error estimate between the sonographic measurements and the regression-estimated pennation angles for the right and left ES were 0.10 and 0.02, respectively. Conclusions Erector spinae muscle activation can be predicted from the changes in fiber pennation during isometric contractions at 33% and 100% of the MVC force. These findings could be essential for developing a regression equation that could estimate the level of muscle activation from changes in the muscle architecture.

Ultrasound of paediatric appendicitis and its secondary sonographic signs: Providing a more meaningful finding

Sonography is an important clinical tool in diagnosing appendicitis in children as it can obviate both exposure to potentially harmful ionising radiation from computed tomography scans and the need for unnecessary appendicectomies. This review examines the diagnostic accuracy of ultrasound in the identification of acute appendicitis, with a particular focus on the the utility of secondary sonographic signs as an adjunct or corollary to traditionally examined criteria. These secondary signs can be important in cases where the appendix cannot be identified with ultrasound and a more meaningful finding may be made by incorporating the presence or absence of secondary sonographic signs. There is evidence that integrating these secondary signs into the final ultrasound diagnosis can improve the utility of ultrasound in cases where appendicitis is expected, though there remains some conjecture about whether they play a more important role in negative or positive prediction in the absence of an identifiable appendix.

The grumpy stump - ultrasound and stump appendicitis

BACKGROUND: Stump appendicitis, the inflammation of an incompletely removed appendix, is a rare clinical presentation. Sonography can be useful in the diagnosis of the condition; by either directly visualising the inflamed stump, or by identifying signs of peri-caecal inflammation that can raise suspicion of the condition. SUMMARY OF WORK: A potential case of stump appendicitis was identified. This prompted a review of literature focused on the incidence of stump appendicitis, utility of ultrasound to identify an inflamed appendiceal stump, and surgical techniques used in appendectomy. SUMMARY OF RESULTS: Stump appendicitis is rare, with as few as 61 cases identified in literature during the last 60 years1. Of the two common techniques of appendectomy, which are ligation and invagination, the former can sometimes leave a residual stump that acts as a potential lumen for the pathophysiological process of appendicitis to recur. Established sonographic criteria for appendicitis also apply to the residual stump. Sonographic secondary signs that suggest the presence of acute appendicitis2 have also been demonstrated in cases of stump appendicitis3, even in the absence of an identifiable stump. DISCUSSION AND CONCLUSIONS: Appendicitis is usually dismissed in patients with a history of appendectomy. Though uncommon, sonographers should be aware of stump appendicitis in post-appendectomy patients that present with right iliac fossa pain from months to decades later. REFERENCE(S) 1. Subramanian A, Liang MK. A 60-year literature review of stump appendicitis: The need for a critical view. Am J Surg; 2012;203(4):503–7. 2. Reddan T, Corness J, Mengersen K, Harden F. Ultrasound of paediatric appendicitis and its secondary sonographic signs: providing a more meaningful finding. J Med Radiat Sci. 2015;DOI: 10.1002/jmrs.154 3. Martínez Chamorro E, Merina Castilla A, Muñoz Fraile B, Koren Fernández L, Borruel Nacenta S. Stump appendicitis: Preoperative imaging findings in four cases. Abdom Imaging. 2013;38(6):1214–9.

Kirjallisuuskatsaus: Eturauhassyövän androgeeniresponsiiviset in vivo -mallit; Kokeellinen osa: Bioluminesenssiin perustuvan ortotooppisen eturauhassyöpämallin optimointi

Eturauhassyöpä on yksi yleisimmistä syövistä länsimaissa. Eturauhassyöpä on yleensä hitaasti kehittyvä tauti. Edetessään se voi kuitenkin muuntua aggressiivisemmaksi ja aiheuttaa metastaaseja, jotka ovat pääasiallisena syynä taudin kuolleisuuteen. Androgeenit ovat merkittäviä tekijöitä eturauhassyövän patogeneesissä ja eturauhassyöpäkudos on useimmiten riippuvainen androgeeneista. Tämän vuoksi hoidon tavoitteena on estää niiden eritys kirurgisella tai kemiallisella kastraatiolla ja/tai estää androgeenien vaikutus antiandrogeeneilla. Eturauhassyöpää sekä sen hoitoon tarkoitettuja uusia lääkehoitomahdollisuuksia tutkitaan kiivaasti. Eturauhassyövän tutkimiseen on kehitetty lukematon määrä erilaisia in vivo -malleja. Koska eturauhassyöpä on yleensä androgeeneille herkkä, kuvaavat androgeeniresponsiiviset eläinmallit ihmisen tautia parhaiten. Eturauhassyövän mallintamiseen in vivo voidaan käyttää eri eläinlajeja, mutta hiiri on ylivoimaisesti käytetyin mallieläin. Immuunipuutteisiin hiiriin voidaan aiheuttaa kasvaimia inokuloimalla ihmisen kasvainsoluja tai osia ihmisen kasvaimista. Ortotooppisesti eturauhaseen inokuloitavat kasvainmallit mallintavat eturauhassyövässä esiintyvää syöpäsolujen ja stroomasolujen välistä epänormaalia vuorovaikutusta. Muuntogeeniset hiirimallit ovat yhä yleisempiä eturauhassyövän tutkimuksessa. Muuntogeenisilla malleilla voidaan mallintaa taudin kehittymistä ja sen etenemistä kokonaisuudessaan parhaiten. Eturauhasessa olevaa kasvainta ja sen kasvua on vaikea seurata ilman prostataspesifisen antigeenin (PSA) pitoisuuden mittausta tai erityisiä kuvantamistekniikoita. Tällaisia menetelmiä, kuten optista kuvantamista, käytetään yhä enemmän hyödyksi erilaisissa eturauhassyövän in vivo -malleissa. Tutkielman kokeellisen osan tavoitteena oli optimoida bioluminesenssiin perustuva optinen kuvantamismenetelmä androgeeniresponsiivisessa LNCaP-luc2-solulinjassa ortotooppisessa eturauhassyöpämallissa. Bioluminesenssikuvantaminen perustuu kasvainsolujen ilmentämän lusiferaasin katalysoimaan reaktioon, jossa entsyymin substraatti, lusiferiini, hapettuu ja tuottaa näkyvää valoa. Lisäksi tavoitteena oli tutkia lääkehoitojen ja kastraation vasteita mallissa. Bioluminesenssiin perustuvalla kuvantamisella oli mahdollista seurata eturauhaskasvainten kasvua noninvasiivisesti, reaaliaikaisesti ja toistuvasti. Bioluminesenssikuvantamisen avulla kasvainten kvantitointi oli nopeampaa kuin ultraäänikuvantamisen avulla, ja kasvainten kasvua oli myös mahdollista seurata useammin kuin seerumin PSA-mittausten avulla. Bioluminesenssikuvantamisen todettiin korreloivan paremmin PSA-pitoisuuden kanssa kuin kasvaimen todelliseen kokoon lopetushetkellä. Seerumin PSA-pitoisuus korreloi kuitenkin bioluminesenssimittausta paremmin eturauhaskasvaimen kokoon tässä kokeessa. Kasvainten oletettua suurempaa kokoa voidaan pitää todennäköisimpänä syynä sille, ettei lääkehoitojen tai kastraation todettu vaikuttavan kasvainten kasvuun bioluminesenssikuvantamisella mitattuna. Bioluminesenssikuvantaminen ei sovellu suurille eikä nekroottisille kasvaimille, sillä kuvantamismenetelmä toimii vain elävillä soluilla. Bioluminesenssikuvantamisen hyödyntämisen kannalta oleellista tässä mallissa on myös lusiferiini-injektion onnistuminen. Jatkotutkimuksia tarvitaan edelleen mallin validoimiseksi mm. lääkehoitojen vasteiden osoittamiseksi.