Tuomas Virén

MINIMALLY INVASIVE ULTRASOUND METHOD FOR INTRA-ARTICULAR DIAGNOSTICS OF CARTILAGE DEGENERATION

Quantitative ultrasound imaging (QUI) can be used to evaluate the integrity of articular cartilage and for diagnosing the early signs of osteoarthritis (OA). In this study, we applied a minimally invasive ultrasound imaging technique and investigated its ability to detect superficial degeneration of bovine knee articular cartilage. Intact (n=13), collagenase-digested (n=6) and mechanically degraded (n=7) osteochondral samples (dia.=25 mm) and custom-made phantoms with different degrees of surface roughness (n=8) were imaged using a high-frequency (40 MHz) QUI system. For each sample and phantom, the ultrasound reflection coefficient (R), integrated reflection coefficient (IRC) and ultrasound roughness index (URI) were determined. Furthermore, to evaluate the clinical applicability of intra-articular ultrasound (IAUS) in diagnostics, one intact bovine knee joint was investigated ex vivo using a simulated arthroscopic approach. Differences in the surface characteristics of the phantoms were detected by monitoring changes in the reflection and surface roughness parameters. Both mechanically- and enzymatically-induced degradation were sensitively diagnosed by decreased (p<0.05) reflection (R and IRC) at the cartilage surface. Furthermore, mechanical degradation was detected in the increased (p<0.05) surface roughness (URI). The intra-articular investigation of a bovine knee joint suggested that the IAUS technique may enable minimally invasive, straightforward diagnostics of the degenerative status of the articular surfaces. We conclude that quantitative IAUS imaging can be used for detecting collagen disruption and increased roughness of the articular surface. This quantitative in vivo ultrasound technique could have great clinical value in the diagnostics of joint diseases.

Quantitative evaluation of spontaneously and surgically repaired rabbit articular cartilage using intra-articular ultrasound method in situ.

During the last decade, a major effort has been devoted to developing surgical methods for repairing localized articular cartilage lesions. Despite some promising results no ultimate breakthrough in surgical cartilage repair has been achieved. Improvements in repair techniques would benefit from more sensitive and quantitative methods for long-term follow-up of cartilage healing. In this study, the potential of a new ultrasound technique for detecting the compositional and structural changes in articular cartilage after surgery, using recombinant human type II collagen gel and spontaneous repair was, investigated. Rabbit knee joints containing intact (n = 13) and surgically (n = 8) or spontaneously (n = 5) repaired tissue were imaged in situ at 6 months after the operation using a clinical intravascular high-frequency (40 MHz) ultrasound device. Based on the ultrasound raw data, ultrasound reflection coefficient (R), integrated ultrasound reflection coefficient (IRC), apparent integrated backscattering coefficient (AIB) and ultrasound roughness index (URI) were determined for each sample. URI was significantly higher in both repair groups than in intact cartilage (p < 0.05). The reflection parameters (R and IRC) were significantly lower in surgically repaired cartilage (p < 0.05) than in intact cartilage. Furthermore, AIB was significantly higher in surgically repaired cartilage than in intact tissue (p < 0.05). To conclude, the integrity of the rabbit articular cartilage repair could be quantitatively evaluated with the nondestructive ultrasound approach. In addition, clinically valuable qualitative information on the changes in cartilage integration, structure and composition could be extracted from the ultrasound images. In the present study, the structure and properties of repaired tissue were inferior to native tissue at 6 months after the operation. The applied ultrasound device and probes are FDA approved and, thus, applicable for the quantitative in vivo evaluation of human articular cartilage.

Comparison of ultrasound and optical coherence tomography techniques for evaluation of integrity of spontaneously repaired horse cartilage

The aim of this study was to compare sensitivity of ultrasound and optical coherence tomography (OCT) techniques for the evaluation of the integrity of spontaneously repaired horse cartilage. Articular surfaces of horse intercarpal joints, featuring both intact tissue and spontaneously healed chondral or osteochondral defects, were imaged ex vivo with arthroscopic ultrasound and laboratory OCT devices. Quantitative ultrasound (integrated reflection coefficient (IRC), apparent integrated backscattering coefficient (AIB) and ultrasound roughness index (URI)) and optical parameters (optical reflection coefficient (ORC), optical roughness index (ORI) and optical backscattering (OBS)) were determined and compared with histological integrity and mechanical properties of the tissue. Spontaneously healed tissue could be quantitatively discerned from the intact tissue with ultrasound and OCT techniques. Furthermore, several significant correlations (p < 0.05) were detected between ultrasound and OCT parameters. Superior resolution of OCT provided a more accurate measurement of cartilage surface roughness, while the ultrasound backscattering from the inner structures of the cartilage matched better with the histological findings. Since the techniques were found to be complementary to each other, dual modality imaging techniques could provide a useful tool for the arthroscopic evaluation of the integrity of articular cartilage.

Tangential volumetric modulated arc therapy technique for left-sided breast cancer radiotherapy

BackgroundThe aim of the present study was to introduce a new restricted tangential volumetric modulated arc therapy (tVMAT) technique for whole breast irradiation and compare its dosimetric properties to other currently used breast cancer radiotherapy techniques.MethodTen consecutive women with left-sided breast cancer were enrolled in this retrospective study. Four treatment plans were generated for each patient: 1) standard tangential field-in-field (FinF), 2) tangential intensity modulated radiotherapy (tIMRT), 3) tangential VMAT (tVMAT) with two dual arcs of 50-60° and 4) continuous VMAT (cVMAT) with a dual arc of 240°. The plans were created with Monaco® (tIMRT, tVMAT and cVMAT) and Oncentra® (FinF) treatment planning systems.ResultsWith both VMAT techniques significantly higher cardiac avoidance, dose coverage and dose homogenity were achieved when compared with FinF or tIMRT techniques (p < 0.01). VMAT techniques also decreased the high dose areas (above 20 Gy) of ipsilateral lung. There were no significant differences in the mean dose of contralateral breast between the tVMAT, tIMRT and FinF techniques. The dose coverage (V47.5 Gy) was greatest with cVMAT. However, with cVMAT the increase of contralateral breast dose was significant.ConclusionsThe present results support the hypothesis that the introduced tVMAT technique is feasible for treatment of left-sided breast cancer. With tVMAT dose to heart and ipsilateral lung can be reduced and the dose homogeneity can be improved without increasing the dose to contralateral breast or lung.

Arthroscopic Ultrasound Assessment of Articular Cartilage in the Human Knee Joint: A Potential Diagnostic Method

Objective: We tested whether an intra-articular ultrasound (IAUS) method could be used to evaluate cartilage status arthroscopically in human knee joints in vivo. Design: Seven patients undergoing arthroscopic surgery of the knee were enrolled in this study. An ultrasonic examination was conducted using the same portals as in the arthroscopic surgery. A high-frequency (40-MHz) ultrasound transducer (diameter = 1 mm) was directed to the desired location on the articular surface under arthroscopic control. In addition to ultrasound data, an IAUS video and optical video through the arthroscope were recorded. Classification of cartilage injuries according to International Cartilage Repair Society, as conducted by the orthopedic surgeon, provided reference data for comparison with the IAUS. Results: The IAUS method was successful in imaging different characteristics of the articular surfaces (e.g., intact surface, surface fibrillation, and lesions of varying depth). In some cases, also the subchondral bone and abnormal internal cartilage structure were visible in the IAUS images. Specifically, using the IAUS, a local cartilage lesion of 1 patient was found to be deeper than estimated arthroscopically. Conclusions: The IAUS method provided a novel arthroscopic method for quantitative imaging of articular cartilage lesions. The IAUS provided quantitative information about the cartilage integrity and thickness, which are not available in conventional arthroscopy. The present equipment is already approved by the Food and Drug Administration for intravascular use and might be transferred to intra-articular use. The invasiveness of the IAUS method might restrict its wider clinical use but combined with arthroscopy, ultrasonic assessment may enlarge the diagnostic potential of arthroscopic surgery.

Arthroscopic optical coherence tomography provides detailed information on articular cartilage lesions in horses.

Arthroscopy enables direct inspection of the articular surface, but provides no information on deeper cartilage layers. Optical coherence tomography (OCT), based on measurement of reflection and backscattering of light, is a diagnostic technique used in cardiovascular surgery and ophthalmology. It provides cross-sectional images at resolutions comparable to that of low-power microscopy. The aim of this study was to determine if OCT is feasible for advanced clinical assessment of lesions in equine articular cartilage during diagnostic arthroscopy. Diagnostic arthroscopy of 36 metacarpophalangeal joints was carried out ex vivo. Of these, 18 joints with varying degrees of cartilage damage were selected, wherein OCT arthroscopy was conducted using an OCT catheter (diameter 0.9 mm) inserted through standard instrument portals. Five sites of interest, occasionally supplemented with other locations where defects were encountered, were arthroscopically graded according to the International Cartilage Repair Society (ICRS) classification system. The same sites were evaluated qualitatively (ICRS classification and morphological description of the lesions) and quantitatively (measurement of cartilage thickness) on OCT images. OCT provided high resolution images of cartilage enabling determination of cartilage thickness. Comparing ICRS grades determined by both arthroscopy and OCT revealed poor agreement. Furthermore, OCT visualised a spectrum of lesions, including cavitation, fibrillation, superficial and deep clefts, erosion, ulceration and fragmentation. In addition, with OCT the arthroscopically inaccessible area between the dorsal MC3 and P1 was reachable in some cases. Arthroscopically-guided OCT provided more detailed and quantitative information on the morphology of articular cartilage lesions than conventional arthroscopy. OCT could therefore improve the diagnostic value of arthroscopy in equine orthopaedic surgery.

Arthroscopic Ultrasound Technique for Simultaneous Quantitative Assessment of Articular Cartilage and Subchondral Bone: An In Vitro and In Vivo Feasibility Study

Traditional arthroscopic examination is subjective and poorly reproducible. Recently, we introduced an arthroscopic ultrasound method for quantitative diagnostics of cartilage lesions. Here we describe our investigation of the feasibility of ultrasound arthroscopy for simultaneous measurements of articular cartilage and subchondral bone. Human osteochondral samples (n = 13) were imaged using a clinical 9-MHz ultrasound system. Ultrasound reflection coefficients (R, IRC), the ultrasound roughness index (URI) and the apparent integrated backscattering coefficient (AIB) were determined for both tissues. Mechanical testing, histologic analyses and micro-scale computed tomography imaging were the reference methods. Ultrasound arthroscopies were conducted on two patients. The ultrasound reflection coefficient correlated with the Mankin score and Youngs modulus of cartilage (|r| > 0.56, p < 0.05). Ultrasound parameters (R, IRC, AIB) for subchondral bone correlated with the bone surface/volume ratio (|r| > 0.70, p < 0.05) and trabecular thickness (|r| > 0.59, p < 0.05). Furthermore, R and subchondral bone mineral density were significantly correlated (|r| > 0.65, p < 0.05). Arthroscopic ultrasound examination provided diagnostically valuable information on cartilage and subchondral bone in vivo.

Ultrasound evaluation of mechanical injury of bovine knee articular cartilage under arthroscopic control

A local cartilage injury can trigger development of posttraumatic osteoarthritis (OA). Surgical methods have been developed for repairing cartilage injuries. Objective and sensitive methods are needed for planning an optimal surgery as well as for monitoring the surgical outcome. In this laboratory study, the feasibility of an arthroscopic ultrasound technique for diagnosing cartilage injuries was investigated. In bovine knees (n = 7) articular cartilage in the central patella and femoral sulcus was mechanically degraded with a steel brush modified for use under arthroscopic control. Subsequently, mechanically degraded and intact adjacent tissue was imaged with a high frequency (40 MHz) intravascular ultrasound device operated under arthroscopic guidance. After opening the knee joint, mechanical indentation measurements were also conducted with an arthroscopic device at each predefined anatomical site. Finally, cylindrical osteochondral samples were extracted from the measurement sites and prepared for histological analysis. Quantitative parameters, i.e., reflection coefficient (R), integrated reflection coefficient (IRC), apparent integrated backscattering (AIB), and ultrasound roughness index (URI) were calculated from the ultrasound signals. The reproducibilities (sCV %) of the measurements of ultrasound parameters were variable (3.7% to 26.1%). Reflection and roughness parameters were significantly different between mechanically degraded and adjacent intact tissue (p <; 0.05). Surface fibrillation of mechanically degraded tissue could be visualized in ultrasound images. Furthermore, R and IRC correlated significantly with the indentation stiffness. The present results are encouraging; however, further technical development of the arthroscopic ultrasound technique is needed for evaluation of the integrity of human articular cartilage in vivo.

Experimental and Analytical Comparisons of Tissue Dielectric Constant (TDC) and Bioimpedance Spectroscopy (BIS) in Assessment of Early Arm Lymphedema in Breast Cancer Patients after Axillary Surgery and Radiotherapy

BACKGROUND Early diagnosis of breast cancer treatment-related lymphedema (BCRL) is of great importance for longstanding treatment results. Tissue dielectric constant (TDC) and bioimpedance spectroscopy (BIS) both have a potential for early diagnosis, but have not been compared. METHODS AND RESULTS One hundred women, treated for breast cancer with breast surgery, axillary dissection, and radiotherapy, were examined within one year after breast cancer treatment, as part of the follow-up procedure. Affected/at-risk and contralateral arms were measured with the TDC technique specific to localized skin water content and the BIS technique assessing arm extracellular fluid (ECF). Thirty-eight patients were clinically diagnosed for lymphedema (38.0%). The sensitivity and specificity for the TDC method were 65.8% and 83.9%, and for BIS method 42.1% and 93.5%, (p < 0.001 and NS), respectively. Of all lymphedema, 18.4% were detected only by TDC and 2.6% by BIS. Affected arm to contralateral arm TDC ratios for upper arm and forearm, 1.56 ± 0.49 and 1.28 ± 0.33, demonstrating the localized feature of the TDC measurements were significantly greater than the BIS arm ratio 1.12 ± 0.12 (both p < 0.001). CONCLUSIONS Discrepancies between TDC and BIS techniques in assessing lymphedema are related to different measurement techniques and assessed tissue water components. Independently of selected technique-specific threshold limit, the TDC technique was more sensitive than the BIS technique in the early assessment of BCRL and demonstrated that nearly 20% of early lymphedema are only superficially localized. The results further supported the complementary role of TDC and arm volume measurements as a highly diagnostic method for early lymphedema.

EFFECTS OF ULTRASOUND BEAM ANGLE AND SURFACE ROUGHNESS ON THE QUANTITATIVE ULTRASOUND PARAMETERS OF ARTICULAR CARTILAGE

High-resolution arthroscopic ultrasound imaging provides a potential quantitative technique for the diagnostics of early osteoarthritis. However, an uncontrolled, nonperpendicular angle of an ultrasound beam or the natural curvature of the cartilage surface may jeopardize the reliability of the ultrasound measurements. We evaluated systematically the effect of inclining an articular surface on the quantitative ultrasound parameters. Visually intact (n = 8) and mechanically degraded (n = 6) osteochondral bovine patella samples and spontaneously fibrillated (n = 1) and spontaneously proteoglycan depleted (n = 1) osteochondral human tibial samples were imaged using a 50-MHz scanning acoustic system. The surface of each sample was adjusted to predetermined inclination angles (0, 2, 5 and 7 degrees ) and five ultrasound scan lines along the direction of the inclination were analyzed. For each scan line, reflection coefficient (R), integrated reflection coefficient (IRC) and ultrasound roughness index (URI) were calculated. Nonperpendicularity of the cartilage surface was found to affect R, IRC and URI significantly (p < 0.05). Importantly, all ultrasound parameters were able to distinguish (p < 0.05) the mechanically degraded samples from the intact ones even though the angle of incidence of the ultrasound beam varied between 0 and 5 degrees among the samples. Diagnostically, the present findings are important because the natural curvature of the articular surface varies, and a perfect perpendicularity between the ultrasound beam and the surface of the cartilage may be challenging to achieve in a clinical measurement.