Alpha‐2 adrenergic stimulation triggers Achilles tenocyte hypercellularity: Comparison between two model systems

The histopathology of tendons with painful tendinopathy is often tendinosis, a fibrosis‐like condition of unclear pathogenesis characterized by tissue changes including hypercellularity. The primary tendon cells (tenocytes) have been shown to express adrenoreceptors (mainly alpha‐2A) as well as markers of catecholamine production, particularly in tendinosis. It is known that adrenergic stimulation can induce proliferation in other cells. The present study investigated the effects of an exogenously administered alpha‐2 adrenergic agonist in an established in vivo Achilles tendinosis model (rabbit) and also in an in vitro human tendon cell culture model. The catecholamine producing enzyme tyrosine hydroxylase and the alpha‐2A‐adrenoreceptor (α_2A AR) were expressed by tenocytes, and alpha‐2 adrenergic stimulation had a proliferative effect on these cells, in both models. The proliferation was inhibited by administration of an α_2A AR antagonist, and the in vitro model further showed that the proliferative alpha‐2A effect was mediated via a mitogenic cell signaling pathway involving phosphorylation of extracellular‐signal‐regulated kinases 1 and 2. The results indicate that catecholamines produced by tenocytes in tendinosis might contribute to the proliferative nature of the pathology through stimulation of the α_2A AR, pointing to a novel target for future therapies. The study furthermore shows that animal models are not necessarily required for all aspects of this research.     

Pathological tendons maintain sufficient aligned fibrillar structure on ultrasound tissue characterization (UTC)

Structural disorganization in the tendon is associated with tendinopathy, with little research investigating whether disorganization overwhelms the overall structural integrity of the tendon. This study investigated the mean cross‐sectional area (CSA) of aligned fibrillar structure as detected by ultrasound tissue characterization (UTC) in the pathological and normal Achilles and patellar tendons. Ninety‐one participants had their Achilles and/or patellar tendons scanned using UTC to capture a three‐dimensional image of the tendon and allow a semi‐quantification of the echopattern. The mean CSA of aligned fibrillar structure (echo type I + II) and disorganized structure (echo type III + IV) was calculated based on UTC algorithms. Each tendon was classified as either pathological or normal based solely on gray‐scale ultrasound. The mean CSA of aligned fibrillar structure was significantly greater (P ≤ 0.001) in the pathological tendon compared with the normal tendon, despite the pathological tendon containing greater amounts of disorganized structure (P ≤ 0.001). A significant relationship was observed between the mean CSA of disorganized structure and anteroposterior diameter of the Achilles (R² = 0.587) and patellar (R² = 0.559) tendons. This study is the first to show that pathological tendons have sufficient levels of aligned fibrillar structure. Pathological tendons may compensate for areas of disorganization by increasing in tendon thickness.     

Chondral metaplasia in calcific insertional tendinopathy of the Achilles tendon.

OBJECTIVE: To ascertain whether tendon samples harvested from patients with calcific insertional Achilles tendinopathy showed features of failed healing response, and whether abnormal quantities of type II collagen had been produced in that area by these tenocytes. DESIGN: Comparative laboratory study. DESIGN: University teaching hospitals. PATIENTS: Tendon samples were harvested from eight otherwise healthy male individuals (average age 47.5+/-8.4 years, range 38 to 60) who were operated for calcific insertional Achilles tendinopathy and from nine male patients who died of cardiovascular events (mean age 63.1+/-10.9 years) while in hospital. INTERVENTIONS: Open surgery for calcific insertional Achilles tendinopathy. MAIN OUTCOME MEASURE: Semi-quantitative histochemical, immunohistochemical, and immunocytochemical methods to ascertain whether tendinopathic tendons were morphologically different from control tendons, and whether abnormal types of collagen were produced. RESULTS: Tenocytes from tendons from patients with calcific insertional Achilles tendinopathy exhibit chondral metaplasia, and produce abnormally high quantities of collagen type II and III. CONCLUSIONS: The altered production of collagen may be one reason for the histopathological alterations described in the present study. Areas of calcific insertional Achilles tendinopathy have been subjected to abnormal loads. These tendons may be less resistant to tensile forces. Further studies should investigate why some tendons undergo these changes.     

Coexistence of up‐regulated NMDA receptor 1 and glutamate on nerves,vessels and transformed tenocytes in tendinopathy

Elevated levels of the neurotransmitter glutamate and the presence of its receptor, N‐methyl‐d ‐aspartate receptor type 1 (NMDAR1), have been established in patients with tendinopathy, i.e. chronic tendon pain and degeneration. However, whether NMDAR1 is up‐ or down‐regulated in tendinopathy and co‐localized with glutamate is still unexplored. We hypothesize that an alteration in tissue expression and in the coexistence of NMDAR1 and glutamate occurs in tendinopathy and might play a role in nociception and possibly also progression of tendon degeneration (tendinosis). We therefore examined the tissue distribution and levels of NMDAR1 and glutamate in biopsies from patients with patellar tendinopathy (n=10) and from controls (n=8). The biopsies were single‐ and double‐stained immunohistochemically for glutamate and NMDAR1 and assessed subjectively and semi‐quantitatively. The chronic painful tendons exhibited a significant elevation of NMDAR1 (ninefold), which was independent of the observed increase in glutamate (10‐fold). This up‐regulation of NMDAR1 and glutamate was found to be co‐localized on nerve fibers as well as on morphologically altered tenocytes and blood vessels. None of the controls exhibited neuronal coexistence of glutamate and NMDAR1. The neuronal coexistence of glutamate and NMDAR1, observed in painful tendinosis but not in controls, suggests a regulatory role in intensified pain signalling.     

Tenocytes from ruptured and tendinopathic achilles tendons produce greater quantities of type III collagen than tenocytes from normal achilles tendons. An in vitro model of human tendon healing

Type I collagen is the main collagen in tendons; type III collagen is present in small amounts. Ruptured Achilles tendons contain a significantly greater proportion of type Ill collagen, which predisposes them to rupture. We used an in vitro model to determine whether tenocytes from Achilles tendons that were ruptured (N = 22), nonruptured (N = 7), tendinopathic (N = 12), and fetal (N = 8) show different behavior. Samples of Achilles tendon were digested with collagenase and the released tenocytes were collected. Primary tenocyte cultures were established and subsequently cultured onto glass coverslips. Once a confluent monolayer was obtained, the cell populations were "wounded" by scraping a pipette tip along the surface. The cultures were further incubated for either 1, 4, 8, 12, 16, or 24 hours, and production of types I and II collagen was assessed by immunostaining. In cultures from ruptured and tendinopathic tendons, there was increased production of type Ill collagen. Athletic participation places excess stress on the Achilles tendon, which could potentially lead to areas of microtrauma within the tendon. These areas may heal by the production of type III collagen, which is an abnormal healing response. Accumulation of such episodes of microtrauma could resuit in a critical point where the resistance of the tissue to tensile forces is compromised and tendon rupture occurs.     

Asymptomatic Achilles,patellar, and quadriceps tendinopathy: A longitudinal clinical and ultrasonographic study in elite fencers

Lower limb tendon changes detected at imaging are common among asymptomatic athletes. We aimed to prospectively assess the clinical status, tendon structure, and vascularity of lower limb tendons of elite fencers, and predict the risk of developing symptoms over time. Clinical examination, changes at ultrasonography (US), and Power Doppler (PD) flow of both the Achilles, patellar, and quadriceps tendon were assessed in 37 elite fencers in January 2007 and 3 years after. Two hundred and twenty‐two tendons were examined. At the last appointment, patellar tendons diagnosed as abnormal at baseline were more likely to develop symptoms than those normal at baseline (P < 0.05, Fisher's exact test), while US and PD abnormalities on Achilles and quadriceps tendons were no predictive for development of symptoms over years. A very low percentage of tendons diagnosed as normal at baseline (1.45%) showed US abnormalities at 3‐year follow‐up. In asymptomatic elite fencers, structural changes are relatively common at US and PD assessment of Achilles, quadriceps, and patellar tendons. It seems unlikely that additional PD investigations provide further information or change prognosis in patients with US diagnosis of tendinopathy.     

Nerve-related characteristics of ventral paratendinous tissue in chronic Achilles tendinosis

Ultrasound and Doppler examination has shown high blood flow-neovascularisation inside and outside the ventral Achilles tendon in chronic painful tendinosis, but not in pain-free normal Achilles tendons. In patients with Achilles tendinosis, injections with the sclerosing substance polidocanol, targeting the areas with increased blood flow, have been demonstrated to give pain relief. A drawback when interpreting these findings is the fact that the pattern of nerve supply in the target area, i.e. the ventral area of the tendon, is so far unknown. In this study, therefore, tissue specimens from this area, obtained during surgical treatment of patients with chronic painful midportion Achilles tendinosis, were examined. In the examined area, containing loose connective tissue, the general finding was a presence of large and small arteries and nerve fascicles. The nerve fascicles were distinguished in sections processed for the pan-neural marker protein gene-product 9.5. The nerve fascicles contain sensory nerve fibers, as shown via staining for the sensory markers substance P (SP) and calcitonin gene-related peptide, and sympathetic nerve fibers as seen via processing for tyrosine hydroxylase. In addition, there were immunoreactions for the SP-preferred receptor, the neurokinin-1 receptor, in blood vessel walls and nerve fascicles. Some of the blood vessels were supplied by an extensive peri-vascular innervation, sympathetic nerve fibers being a distinct component of this innervation. There was also a marked occurrence of immunoreactions for the α₁-adrenoreceptor in arterial walls as well as in the nerve fascicles. Altogether, these findings suggest that the area investigated is under marked influence by the nervous system, including sympathetic and sensory components. Thus, sympathetic/sensory influences may be involved in the pain mechanisms from this area. In conclusion, the nerve-related characteristics of the area targeted by the polidicanol injection treatment for Achilles tendinosis, are shown here for the first time.     

The influence of physical activity during youth on structural and functional properties of the Achilles tendon

Achilles tendinopathy is a highly prevalent sports injury. Animal studies show a growth response in tendons in response to loading in the immature phase but not after puberty maturation. The aim of this investigation was to examine the structural and material properties in long distance runners who were either physically active (HAY) or inactive (LAY) in young age. Twelve men in HAY group and eight men in LAY group participated. Structural, functional, and biochemical properties of Achilles tendon were estimated from magnetic resonance imaging, ultrasound video recordings, mechanical tests, and tendon biopsies, respectively. There was no difference between the groups with respect to tendon cross‐sectional area or tendon free length. There was no difference between the groups with respect to maximal force or mechanical properties. The collagen content, enzymatic and nonenzymatic cross‐link density did not differ between the groups, nor did collagen fibril density, diameter, and area. There was a correlation between age and pentosidine/collagen within the groups [(HAY: P < 0.05 and r² = 0.47) and (LAY: P < 0.05 and r² = 0.52)]. The data suggest that high or low activity during youth did not appreciably influence the mechanical, structural, or biochemical properties of the Achilles tendon in adult long distance runners.     

Blood flow of the Achilles tendon during military training

The purpose of this study was to evaluate the vascular response of the Achilles tendon as indicated by power Doppler activity during a military training program of 6 weeks. 49 male military recruits (98 tendons) volunteered for this study. Before and during the military training program, the Achilles tendons were screened with gray-scale ultrasonography and power Doppler US. Reactive tendinopathies of the Achilles tendons were registered by means of a clinical examination, VAS-scores and VISA-A scores. The US examination, the clinical examination, VAS-scores and VISA-A scores showed that 13/98 tendons developed a reactive tendinopathy. 3 of these 13 symptomatic tendons showed intratendinous Doppler activity. In these tendons, pain was always present before the vascular response of the Achilles tendon. Both pain and hypervascularisation remained visible till the end of the basic military training. In 5 asymptomatic tendons with no structural changes of the tendon, a vascular response was seen during one single measurement. It can be hypothesized that there is no relationship between the vascular response of the Achilles tendon and the pain in a reactive tendinopathy. In a reactive tendinopathy, other pain mechanisms must be investigated in future research.     

Achilles tendon and paratendon microcirculation in midportion and insertional tendinopathy in athletes

BACKGROUND: Neovascularisation can be detected qualitatively by Power Doppler in Achilles tendinopathy. Quantitative data regarding tendon microcirculation have not been established and may be substantial. PURPOSE: To assess the microcirculation of the Achilles tendon and the paratendon in healthy volunteers as well as in athletes with either midportion or insertional tendinopathy. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: In 66 physically active volunteers, parameters of Achilles tendon and paratendon microcirculation, such as tissue oxygen saturation, relative postcapillary venous filling pressures, and microcirculatory blood flow, were determined at rest at 2-mm and 8-mm tissue depths. Forty-one patients never had Achilles pain (25 men, 27 +/- 8 years), 14 patients had insertional pain (7 men, 29 +/- 8 years), and 11 patients had midportion tendinopathy (7 men, 38 +/- 13 years, not significant). RESULTS: Achilles tendon diameter 2 cm and 6 cm proximal to the insertion was increased in symptomatic tendons. Compared with the uninvolved opposite tendon, deep microcirculatory blood flow was significantly elevated at insertional (160 +/- 79 vs 132 +/- 42, P < .05) as well as in midportion tendinopathy (150 +/- 74 vs 119 +/- 34, P < .05). The microcirculation in the uninvolved opposite tendon and the normal athlete controls were not significantly different from each other (132 +/- 42 insertional asymptomatic vs 119 +/- 34 mid-portion vs 120 +/- 48 healthy tendon). Insertional paratendon deep microcirculatory flow was elevated in all groups, whereas tissue oxygen saturation and relative postcapillary venous filling pressures were not significantly different. CONCLUSION: Microcirculatory blood flow is significantly elevated at the point of pain in insertional and midportion tendinopathy. Postcapillary venous filling pressures are increased at both the midportion Achilles tendon and the midportion paratendon, whereas tissue oxygen saturation is not different among the studied groups. We found no evidence of an abnormal microcirculation of the asymptomatic limb in Achilles tendinopathy.     

The COL12A1 and COL14A1 genes and Achilles tendon injuries

Genes encoding for tenascin C and a subunit of type V collagen have previously been reported to be associated with Achilles tendon injuries. Types XII and XIV collagen may be involved in similar biological processes as these proteins in tendons. The aim of this study was therefore to test the association between polymorphisms within COL12A1 and COL14A1 and Achilles tendon injuries. Restriction fragment length polymorphism (RFLP) analysis was used to identify the relative frequencies of two polymorphisms within each of the COL12A1 and COL14A1 genes within 137 subjects with clinical symptoms of Achilles tendon injuries, consisting of 93 with Achilles tendinopathy and 44 with Achilles tendon rupture, and 131 asymptomatic control subjects. No statistically significant differences were identified in the genotype, allele or haplotype distributions between the affected and control subjects. The findings from this study suggest that although COL12A1 and COL14A1 are involved in similar biological processes as TNC and COL5A1, the polymorphisms tested are not associated with clinical symptoms of Achilles tendon injury within the investigated population.     

Applying physical science principles to mid‐substance Achilles tendinopathy and the relationship to eccentric lengthening exercises

Mid‐substance Achilles tendinopathy is common in the active population. Eccentric (lengthening) exercises are known to be effective in alleviating the clinical condition. To better understand mid‐substance Achilles tendinopathy and the response to lengthening exercises physical science principles of elasticity are applied. We apply elastic motion laws to the spring‐like tendon as well as the normal and pathological adaptation seen with this common injury. We will validate important assumptions of the spring‐like behavior of the tendon and then apply these findings to the injured and rehabilitating states. Our analysis considers that the tendon can be viewed as being spring‐like with elasticity principles being applicable and the force exerted on the tendon during lengthening is primarily in a uniaxial direction. This applied lengthening force results in tendon mechanical and structural adaptation. Injury, and ultimately the clinical condition, occurs when the applied force exceeds the ability of the tendon to normally adapt. Morphological changes of the injured tendon are an attempt by the body to make the tendon more compliant. Lengthening exercises can be assessed as achieving this task with an improvement of tendon compliance. Physical science analysis proposes that the preferred rehabilitation tendon pathway is to try and decrease tendon stiffness to allow for more tendon lengthening. The body's morphological alterations of the pathological tendon are also consistent with this approach. For mid‐substance Achilles tendinopathy, this adaptation of decreased stiffness ultimately increases the tendons ability to withstand applied force during lengthening.     

Achilles tendon structure improves on UTC imaging over a 5‐month pre‐season in elite Australian football players

Pre‐season injuries are common and may be due to a reintroduction of training loads. Tendons are sensitive to changes in load, making them vulnerable to injury in the pre‐season. This study investigated changes in Achilles tendon structure on ultrasound tissue characterization (UTC) over the course of a 5‐month pre‐season in elite male Australian football players. Eighteen elite male Australian football players with no history of Achilles tendinopathy and normal Achilles tendons were recruited. The left Achilles tendon was scanned with UTC to quantify the stability of the echopattern. Participants were scanned at the start and completion of a 5‐month pre‐season. Fifteen players remained asymptomatic over the course of the pre‐season. All four echo‐types were significantly different at the end of the pre‐season, with the overall echopattern suggesting an improvement in Achilles tendon structure. Three of the 18 participants developed Achilles tendon pain that coincided with a change in the UTC echopattern. This study demonstrates that the UTC echopattern of the Achilles tendon improves over a 5‐month pre‐season training period, representing increased fibrillar alignment. However, further investigation is needed to elucidate with this alteration in the UTC echopattern results in improved tendon resilience and load capacity.     

Prevalence of Achilles and patellar tendinopathy and their association to intratendinous changes in adolescent athletes

Achilles (AT) and patellar tendons (PT) are commonly affected by tendinopathy in adult athletes but prevalence of symptoms and morphological changes in adolescents is unclear. The study aimed to determine prevalence of tendinopathy and intratendinous changes in ATs and PTs of adolescent athletes. A total of 760 adolescent athletes (13.0 ± 1.9 years; 160 ± 13 cm; 50 ± 14 kg) were examined. History, local clinical examination, and longitudinal Doppler ultrasound analysis for both ATs and PTs were performed including identification of intratendinous echoic changes and vascularization. Diagnosis of tendinopathy was complied clinically in case of positive history of tendon pain and tendon pain on palpation. Achilles tendinopathy was diagnosed in 1.8% and patellar tendinopathy in 5.8%. Vascularizations were visible in 3.0% of ATs and 11.4% of PTs, hypoechogenicities in 0.7% and 3.2% as well as hyperechogenicities in 0% and 0.3%, respectively. Vascularizations and hypoechogenicities were statistically significantly more often in males than in females (P ≤ 0.02). Subjects with patellar tendinopathy had higher prevalence of structural intratendinous changes than those without PT symptoms (P ≤ 0.001). In adolescent athletes, patellar tendinopathy is three times more frequent compared with Achilles tendinopathy. Longitudinal studies are necessary to investigate physiological or pathological origin of vascularizations and its predictive value in development of tendinopathy.     

Relationship between neovascularization and clinical severity in Achilles tendinopathy in 556 paired measurements

Neovascularization is frequently observed in tendinopathy. Previous studies have focused on the role of neovascularization in Achilles tendinopathy, but have been conducted in small series. It is still unclear whether the degree of neovascularization is related to severity of symptoms. The purpose was to study the relationship between ultrasonographic neovascularization and clinical severity in patients with Achilles tendinopathy. In this prospective cohort study, data on 127 patients (141 tendons) were assembled from databases of three clinical trials. All patients followed an eccentric exercise program. The Öhberg neovascularization score (0–4+) and Victorian Institute of Sports Assessment‐Achilles (VISA‐A) score (split into domains: pain, function and activity) were collected during baseline and follow‐up. The relationship between neovascularization and VISA‐A score was calculated. At baseline, 107 tendons (76%) showed some degree of neovascularization. In 556 coupled measurements, neovascularization was weakly related to the VISA‐A score [Exp (B) 1.017, 95% confidence interval (CI), 1.007–1.026]. No significant relationship was found between neovascularization and the pain domain (P = 0.277) and the activity domain (P = 0.283), but there was between neovascularization and the function domain of the VISA‐A score [Exp (B) = 1.067, 95% CI 1.018–1.119]. In conclusion, neovascularization in Achilles tendinopathy is weakly related to clinical severity, mainly based on the function domain of the VISA‐A score.     

Trigger finger,tendinosis, and intratendinous gene expression

The pathogenesis of trigger finger has generally been ascribed to primary changes in the first annular ligament. In contrast, we recently found histological changes in the tendons, similar to the findings in Achilles tendinosis or tendinopathy. We therefore hypothesized that trigger finger tendons would show differences in gene expression in comparison to normal tendons in a pattern similar to what is published for Achilles tendinosis. We performed quantitative real‐time polymerase chain reaction on biopsies from finger flexor tendons, 13 trigger fingers and 13 apparently healthy control tendons, to assess the expression of 10 genes which have been described to be differently expressed in tendinosis (collagen type 1a1, collagen 3a1, MMP‐2, MMP‐3, ADAMTS‐5, TIMP‐3, aggrecan, biglycan, decorin, and versican). In trigger finger tendons, collagen types 1a1 and 3a1, aggrecan and biglycan were all up‐regulated, and MMP‐3and TIMP‐3 were down‐regulated. These changes were statistically significant and have been previously described for Achilles tendinosis. The remaining four genes were not significantly altered. The changes in gene expression support the hypothesis that trigger finger is a form of tendinosis. Because trigger finger is a common condition, often treated surgically, it could provide opportunities for clinical research on tendinosis.     

The role of vasculature and angiogenesis for the pathogenesis of degenerative tendons disease

More than 100 years ago Wilhelm Roux (1895) introduced the term "functional adaptation to anatomy and physiology". Compared with other organ systems the functional adaptation processes are best identifiable in the locomotor system, like for example in the two types of tendons: traction and gliding tendons. Traction tendons are tendons where the direction of pull is in line with the direction of the muscle (e.g. Achilles tendon). Gliding tendons (e.g. tibialis posterior tendon) change direction by turning around a bony or fibrous hypomochlion. In this region the tendon is subjected to intermittent compressive and shear forces and the extracellular matrix consists of avascular fibrocartilage. Avascularity is considered to be a key factor for the etiology of degenerative tendon disease. The repair capability after repetitive microtrauma is strongly compromised in avascular tissue of gliding tendons. Reduced vascularity is not a specific feature of gliding tendons; several studies have shown that the number and size of blood vessels are largely shortened in the waist of the Achilles tendon. However, histological biopsies from degenerated Achilles tendons and Doppler flow examinations revealed a high blood vessel density in patients with degenerative tendon disease. Angiogenesis is mediated by angiogenic factors and recent studies have shown that the vascular endothelial growth factor (VEGF) is highly expressed in degenerative Achilles tendons, whereas VEGF expression is nearly completely downregulated in healthy tendons. Several factors are able to upregulate VEGF expression in tenocytes: hypoxia, inflammatory cytokines and mechanical load. Since VEGF has the potential to stimulate the expression of matrix metalloproteinases and inhibit the expression of tissue inhibitors of matrix metalloproteinases tissue inhibitor of metalloproteinases (TIMP) in various cell types (e.g. endothelial cells, fibroblasts, chondrocytes), this cytokine might play a significant role for the pathogenetic processes during degenerative tendon disease. An animal experiment in the rabbit has shown that local injection of VEGF reduced the material properties of the Achilles tendon. These experimental findings are in accordance with clinical results that a locally administered (in the area with neovascularization) sclerosing drug (Polidocanol) has a beneficial effect on chronic mid-portion Achilles tendinosis. In conclusion, decreased and increased vascularity might be involved in the pathogenesis of degenerative Achilles tendon disease.     

Achilles tendon pain intensity and level of neovascularization in athletes as determined by color Doppler ultrasound

The cause of pain in Achilles tendinopathy is thought to be related to the presence of neovascularization in the tendon as seen on color Doppler ultrasound. Asymptomatic pathology has been observed in patellar tendons of elite athletes. The purpose of this study was to examine the prevalence of Achilles tendon pain and the characteristics of Achilles tendons in a young athletic population. Sixty-four varsity athletes underwent color Doppler ultrasound imaging to determine tendon thickness, presence of degeneration and neovascularization. The presence of swelling and tenderness was determined, and Achilles tendon pain was rated on three visual analogue scales (VAS) (pain during exercise, pain at rest, pain during daily activities) as well as on the VISA-A scale. Tendon symptoms were not related to the presence of neovascularization. There was a low prevalence of Achilles tendinopathy, tenderness, and neovascularization in this population. Neovascularization was seen in both a painful and a non-painful tendon.     

Doppler ultrasound signal in Achilles tendinopathy reduces immediately after activity

BACKGROUND: A relationship has been identified between vascularization on Doppler ultrasound (Doppler signal) and Achilles tendon pain. Doppler signal may increase minutes after prolonged activity, but the immediate effect is unknown. The aim of the study was to investigate the immediate effect of short term activity on Achilles tendon Doppler signal. Achilles tendinopathy patients (7 patients, 10 tendons) and asymptomatic controls (6 controls, 12 tendons) performed 2 activity tasks; a 2 minute continuous step task and one minute continuous calf raise task. Doppler signal was measured at rest and within a minute after each activity. The presence of Doppler signal was quantified using both semi quantitative (modified Ohberg scale; 0=no signal, 5 = > 90% of pathological area contains Doppler signal) and quantitative methods (pixel number). Doppler signal was present in 90% of symptomatic individuals and in none of the asymptomatic controls. The modified Ohberg scale and pixel number reduced significantly after both activity tasks and heart rate increased significantly (p < 0.05). Doppler signal in Achilles tendinopathy may decrease immediately after activities that load the calf muscle and increase heart rate, suggesting that this activity should be avoided prior to imaging to avoid false negative results.     

Magnetic resonance imaging in chronic Achilles tendinopathy.

The main objective of this thesis was to evaluate and monitor the morphological response following treatment interventions in patients with chronic Achilles tendinopathy by using different MRI techniques. For this purpose, we investigated different types of sequences, including gadolinium contrast medium-enhanced T1-WI images (CME T1-WI), and developed a precise method to measure tendon volume and mean intratendinous signal of the Achilles tendon. Study I aimed at evaluating 15 patients with chronic, painful Achilles tendinosis, before and 2 years after surgical treatment. There was marked regression of the intratendinous signal postoperatively. The most sensitive sequence for depicting an intratendinous lesion in this study was CME T1-WI images. They showed a regression of the intratendinous signal abnormality from 13/15 patients preoperatively to 4/15 postoperatively. The clinical outcome was excellent in eight, good in five, fair in one and poor in one patient. In study II, the early contrast agent enhancement in the dynamically enhanced MRI signal (DEMRI) was correlated with the histopathologic findings in 15 patients with chronic Achilles tendinopathy. Early contrast enhancement (within the first 72s) was seen in DEMRI in the symptomatic Achilles tendons, with a significant difference compared to the asymptomatic contralateral tendons. Increased severity of tendon changes, including fiber structure abnormality, increased vascularity, rounding of nuclei, and increased amount of glycosaminoglycans, correlated to CME. In study III, we developed a computerized 3-D seed-growing MRI technique to measure tendon volume and mean intratendinous signal. This technique showed an excellent inter- and intra-observer reliability. The technique was also used to follow up prospectively the tendon adaptation and healing described in studies IV-VI. In study IV, using serial MRI during a period of 1 year, we evaluated the biological effect of tendon repair following iatrogenic tendon injury by five transversal ultrasound-guided core biopsies employing a needle technique in chronic Achilles tendinopathy. Alterations found during healing, such as tendon volume and intratendinous reactive changes, could be monitored by MR imaging, and subsided as noted in the 7- and 12-month follow-ups. In study V, we evaluated the effect of treatment with a 3-month, daily performed, heavy-loaded calf-muscle strength training program in 25 patients who had been suffering from chronic, painful Achilles tendinopathy. Tendon volume decreased by 14%, and the mean intratendinous signal by 23%. The clinical outcome was improved. In study VI, we revealed tendon adaptation immediately following calf-muscle strength training. An MRI examination within 30min of the performed exercises resulted in increased total tendon volume (12%) and mean intratendinous signal (31%). CONCLUSION: MRI techniques can be used as an adjunct to clinical evaluation by monitoring morphological effects following different treatment interventions, thereby adding evidence in clinical studies on patients with chronic Achilles tendinopathy.