Download PDF
Tierarztl Prax Ausg K Kleintiere Heimtiere 2008; 36(04): 249-262
DOI: 10.1055/s-0038-1622684
HUND/KATZE
Schattauer GmbH

Magnetresonanztomographie von Skelettmuskulatur und Sehnen in der Kleintiermedizin[*]

Untersuchungstechnik und Erscheinungsbild verschiedener Erkrankungen sowie traumatischer VeränderungenMagnetic resonance imaging of musculature and tendons in small animal practice.Imaging technique and appearance of different diseases and traumatic injuries
A. Brühschwein
1   Chirurgische und Gynäkologische Kleintierklinik (Vorstand: Prof. Dr. U. Matis) der Ludwig-Maximilians-Universität München
,
K. Flatz
1   Chirurgische und Gynäkologische Kleintierklinik (Vorstand: Prof. Dr. U. Matis) der Ludwig-Maximilians-Universität München
,
M. Zöllner
1   Chirurgische und Gynäkologische Kleintierklinik (Vorstand: Prof. Dr. U. Matis) der Ludwig-Maximilians-Universität München
,
R. Köstlin
1   Chirurgische und Gynäkologische Kleintierklinik (Vorstand: Prof. Dr. U. Matis) der Ludwig-Maximilians-Universität München
,
U. Matis
1   Chirurgische und Gynäkologische Kleintierklinik (Vorstand: Prof. Dr. U. Matis) der Ludwig-Maximilians-Universität München
› Author Affiliations
Further Information

Publication History

Eingegangen:06 November 2007

akzeptiert:18 June 2008

Publication Date:
04 January 2018 (online)

    Permissions and Reprints

Zusammenfassung:

In einer retrospektiven Analyse der MRT-Untersuchungen von Hundeund Katzenpatienten der Chirurgischen und Gynäkologischen Kleintierklinik der LMU München wurde nach Patienten gesucht, bei denen MR-Signalveränderungen im Muskelparenchym oder in Sehnen chirurgisch, zytologisch oder histopathologisch bestätigt werden konnten. Die Untersuchungen wurden hinsichtlich Untersuchungstechnik sowie MR-Erscheinungsbild verschiedener Erkrankungen und traumatischer Veränderungen des Muskelund Sehnengewebes evaluiert. Fettsupprimierende und flüssigkeitssensitive Sequenzen sowie T1-gewichtete Bilder mit Fettsuppression nach Kontrastmittelgabe sind für die Interpretation des Muskelund Sehnengewebes besonders hilfreich. Neben den Folgen schwerer Muskelund Sehnentraumata, die mit morphologischen Architekturveränderungen einhergehen, lassen sich MR-Signalveränderungen des Muskelparenchyms ohne Zusammenhangstrennungen in drei Gruppen einteilen. Veränderungen mit Muskelödem, z. B. als Folge geringgradiger Traumata oder bei Myositiden, zeigen in flüssigkeitssensitiven Sequenzen eine diffuse Signalsteigerung, während in T1-gewichteten Sequenzen Signalveränderungen fehlen. Hochgradige Muskelatrophien mit diffuser Fettinfiltration weisen als Charakteristikum eine generalisierte Signalanhebung in der Muskulatur in T1und T2-gewichteten Sequenzen auf. Davon abzugrenzen sind raumfordernde Strukturen wie intramuskuläre Hämatome, Abszesse oder Neoplasien, die die normale Architektur und Textur des Muskelparenchyms verändern und unterschiedliche Signalcharakteristika aufweisen können. Da sich die MR-Erscheinungsbilder einzelner Erkrankungen in einer Gruppe stark überschneiden können, ist eine definitive Diagnose anhand der MR-Signalveränderungen allein oft nicht zu stellen. Zusammen mit Anamnese und klinischen Befunden ergibt sich aber meist eine Verdachtsdiagnose. Ferner können die Veränderungen mit der MRT klar lokalisiert und Ausdehnung sowie Grad visualisiert werden, was eine gezielte Biopsie und dadurch eine histologische Diagnose ermöglicht.

Summary

A retrospective study was performed in the Clinic of Small Animal Surgery and Reproduction of the Ludwig Maximilian University Munich. MR-examinations and MR-reports of dogs and cats were reviewed for findings in muscles and tendons that were confirmed by surgery, cytology or histopathology. Imaging techniques and MR-appearances of normal and diseased muscles and tendons were assessed. Fluid sensitive sequences combined with fat suppression techniques and T1-weighted fat suppressed images after application of contrast medium are most valuable for the detection and interpretation of lesions in muscles and tendons. In addition to severe muscle and tendon trauma, which is associated with morphologic architectural changes, there are three general types of magnetic resonance signal changes in the musculature. Edematous changes are seen as a diffuse increase in signal intensity in fluid-sensitive sequences without signal changes in T1-weighted images and may be found as a result of minor trauma, myositis or myopathy. Severe muscle atrophy with concurrent diffuse fatty infiltration shows a characteristic generalized signal increase of the musculature in T1und T2-weighted sequences. This needs to be distinguished from masses such as intramuscular haematomas, abscesses or neoplasia that change normal muscle architecture and can have varying signal characteristics. Due to overlapping of appearance of many diseases in MRI, it is often not possible to make a specific diagnosis by signal changes in the musculature. However, in combination with the history and the results of physical examination a tentative diagnosis can often be made. Furthermore, magnetic resonance imaging enables clear localization and visualization of the size and severity of the changes. This facilitates a targeted biopsy and histopathologic diagnosis.

Schlüsselwörter

Magnetresonanztomographie - MRT - Myopathien - Tendopathien - Hund - Katze

Key words

Magnetic resonance imaging - MRI - myopathies - tendinopathies - trauma - dog - cat

* * Herrn Prof. Dr. Dr. h. c. mult. H. Bostedt zum 70. Geburtstag gewidmet.


 

  • Literatur

  • 1 Allkemper T. Blutungen. In: Klinische MR-Bildgebung. Reimer P, Parizel PM, Stichnoth FA. Hrsg Berlin, Heidelberg, New York: Springer; 2000
    Google Scholar
  • 2 Baltzer WI. et al. Dystrophin-deficient muscular dystrophy in a Weimaraner. J Am Anim Hosp Assoc 2007; 43: 227-232
    CrossrefPubMedGoogle Scholar
  • 3 Bar-Am Y, Anug AM, Shahar R. Femoral compartment syndrome due to haemangiosarcoma in the semimembranosus muscle in a dog. J Small Anim Pract 2006; 47: 286-289
    CrossrefPubMedGoogle Scholar
  • 4 Barber JS, Trees AJ. Clinical aspects of 27 cases of neosporosis in dogs. Vet Rec 1996; 139: 439-443
    CrossrefPubMedGoogle Scholar
  • 5 Bergman RL. et al. Dystrophin-deficient muscular dystrophy in a Labrador Retriever. J Am Anim Hosp Assoc 2002; 38: 255-261
    CrossrefPubMedGoogle Scholar
  • 6 Bilzer T. et al. Myopathie der Labrador Retriever: neuromuskuläre Veränderungen bei kranken und klinisch gesunden Hunden. Tierärztl Prax 2004; 32 (K) 130-139
    PubMedGoogle Scholar
  • 7 Blankenbaker DG, De Smet AA. MR Imaging of muscle injuries. Appl Radiol 2004; 33 (04) 14-26
    PubMedGoogle Scholar
  • 8 Bleedorn JA, Towle HA, Breur GJ, Rohleder JJ. What is your diagnosis? Avulsion of the popliteal tendon. J Am Vet Med Assoc 2006; 229 (12) 1885-1886
    CrossrefPubMedGoogle Scholar
  • 9 Blott S. Disorders of the sceletal muscle – canine. In: Textbook of Veterinary Internal Medicine. 6th ed. Ettinger SJ, Feldmann EC. eds Philadelphia: Elsevier Saunders; 2005: 901-905
    Google Scholar
  • 10 Brofman PJ, Thrall DE. Magnetic resonance imaging findings in a dog with caudal aortic thromboembolism and ischemic myopathy. Vet Radiol Ultrasound 2006; 47 (04) 334-338
    CrossrefPubMedGoogle Scholar
  • 11 Busoni V, Snaps F. Effect of deep digital flexor tendon orientation on magnetic resonance imaging signal intensity in isolated equine limbs – The magic angle effect. Vet Radiol Ultrasound 2002; 43 (05) 428-430
    CrossrefPubMedGoogle Scholar
  • 12 Bydder M, Rahal A, Fullerton GD, Bydder GM. The Magic Angle Effect: A Source of Artifact, Determinant of Image Contrast, and Technique for Imaging. J Magn Reson Imaging 2007; 25: 290-300
    CrossrefPubMedGoogle Scholar
  • 13 Carpenter JL, Hoffman EP, Romanul FCA. et al. Feline muscular dystrophy with dystrophin deficiency. Am J Pathol 1989; 135: 909-919
    PubMedGoogle Scholar
  • 14 Crassm JR. et al. Magnetic resonance, ultrasound and histopathologic correlation of acute and healing equine tendon injuries. Vet Radiol Ultrasound 1992; 33 (04) 206-216
    CrossrefPubMedGoogle Scholar
  • 15 Darke PG, McCullagh KG, Geldart PH. Myasthenia gravis, thymoma and myositis in a dog. Vet Rec 1975; 97: 392-393
    PubMedGoogle Scholar
  • 16 Dennis JM, Alexander RW. Nutritional myopathy in a cat. Vet Rec 1982; 111: 195-196
    CrossrefPubMedGoogle Scholar
  • 17 Dennis JM. et al. Assessment of necropsy findings in sled dogs that died during Iditarod Trail sled dog races: 23 cases 1994-2006. JAVMA 2008; 232 (04) 564-573
    CrossrefPubMedGoogle Scholar
  • 18 De Schepper AM. et al. Muskuloskelettales System. In: Klinische MR-Bildgebung. Reimer P, Parizel PM, Stichnoth FA. Hrsg Berlin, Heidelberg, New York: Springer; 2000
    Google Scholar
  • 19 Eaton-Wells RD, Plummer GV. Avulsion of the popliteal muscle in an Afghan Hound. J Small Anim Pract 1978; 19 (012) 743-747
    CrossrefPubMedGoogle Scholar
  • 20 Evans J, Levesque D, Shelton GD. Canine inflammatory myopathies: a clinicopathological review of 200 cases. J Vet Intern Med 2004; 18 (05) 679-691
    CrossrefPubMedGoogle Scholar
  • 21 Feliu-Pascual AL. et al. Inherited myopathy of great Danes. J Small Anim Pract 2006; 47: 249-254
    CrossrefPubMedGoogle Scholar
  • 22 Fitch RB, Wilson ER, Hathcock JT, Montgomery RD. Radiographic, computed tomographic and magnetic resonance imaging evaluation of a chronic long digital extensor tendon avulsion in a dog. Vet Radiol Ultrasound 1997; 38 (03) 177-181
    CrossrefPubMedGoogle Scholar
  • 23 Frank JR. et al. Systemic arterial dirofilariasis in five dogs. J Vet Intern Med 1997; 11: 189-194
    CrossrefPubMedGoogle Scholar
  • 24 Frannson BA, Gavin PR, Lahmers KK. Supraspinatus tendinosis associated with biceps brachii tendon displacement in a dog. JAVMA 2005; 227 (09) 1429-1433
    CrossrefPubMedGoogle Scholar
  • 25 Garcia J. MRI in inflammatory myopathies. Skeletal Radiol 2000; 29: 425-438
    CrossrefPubMedGoogle Scholar
  • 26 Gaschen FP, Jones BR. Feline myopathies. In: Textbook of Veterinary Internal Medicine. 6th ed. Ettinger SJ, Feldmann EC. eds Philadelphia: Elsevier Saunders; 2005: 906-912
    Google Scholar
  • 27 Gregg A, Bogosb MD, John V, Crues Ill MD, Franklin G, Moser MD. MRImaging in the evaluation of trauma. Emerg Radiol 1994; 1 (01) 1-14
    CrossrefPubMedGoogle Scholar
  • 28 Grundmann S, Montavon PM. Stenosing tenosynovitis of the abductor pollicis longus muscle in dogs. Vet Comp Orthop Traumatol 2001; 14: 95-100
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Gossger NP. Bildgebende Verfahren in der Diagnostik von Myopathien. Dissertation, Würzburg: 2005
    Google Scholar
  • 30 Grappendorf H, Denner J. Eosinophile Myositis. Diagnosesicherung und Abgrenzung der Differentialdiagnosen mittels MRT. Kleintiermedizin, März/April: 2003: 65-68
    Google Scholar
  • 31 Hafner A, Dahme E. Skelettmuskel. In: Grundriss der speziellen pathologischen Anatomie der Haustiere. Stuttgart: Enke; 1999: 343-356
    Google Scholar
  • 32 Hewicker-Trautwein M, Läkamp A, Beckold EM, Gerdwilker A, Nolte I, Meyer-Lindenberg A. Polyarthritis-Polymyositis-Syndrom bei einem sechs Monate alten Deutsch Stichelhaar. Tierärztl Prax 2008; 36 (K) 47-54
    PubMedGoogle Scholar
  • 33 Hicks DG. et al. Imaging Diagnosis – Corpus cavernosum, ischiocavernosus and bulbospongiosus muscle injury in a dog. Vet Radiol Ultrasound 2007; 48 (03) 239-242
    CrossrefPubMedGoogle Scholar
  • 34 Imhof, et al. Gelenke. In: Klinische MR-Bildgebung. Reimer P, Parizel PM, Stichnoth FA. Hrsg Berlin, Heidelberg, New York: Springer; 2000
    Google Scholar
  • 35 Innes JF, Brown G. Rupture of the biceps brachii tendon sheath in two dogs. J Small Anim Pract 2004; 45: 25-28
    CrossrefPubMedGoogle Scholar
  • 36 Joseph RJ, Carillo JM, Lennon VA. Myasthenia Gravis in the Cat. J Vet Intern Med 1988; 2: 75-79
    CrossrefPubMedGoogle Scholar
  • 37 Köpke M, Grevel V, Jurina K, Kiefer I, Schüppel KF. Myositis ossificans bei einer Dobermann-Hündin. Tierärztl Prax 2003; 31 (K) 225-233
    PubMedGoogle Scholar
  • 38 Kornegay JN, Tuler SM, Miller DM. et al. Muscular dystrophy in a litter of golden retriever dogs. Muscle Nerve 1988; 11: 1056-1064
    CrossrefPubMedGoogle Scholar
  • 39 Kraft S. et al. Magnetic resonance imaging characteristics of peripheral nerve sheath tumors of the canine brachial plexus in 18 dogs. Vet Radiol Ultrasound 2007; 48 (01) 1-7
    CrossrefPubMedGoogle Scholar
  • 40 Kramer M, Gerwing M, Hach V, Schimke E. Sonography of the Musculoskeletal System in Dogs and Cats. Vet Radiol Ultrasound 1997; 38 (02) 139-149
    CrossrefPubMedGoogle Scholar
  • 41 Kramer M, Gerwing M, Sheppard C, Schimke E. Ultrasonography for the diagnosis of diseases of the tendon and tendon sheath of the biceps brachii muscle. Vet Surg 2001; 30 (01) 64-71
    CrossrefPubMedGoogle Scholar
  • 42 Kramer M, Schimke E, Gerwing M, Schleich S, Michele U. Achillessehnenerkrankungen bei Hund und Katze. Tierarztl Prax 1998; 26 (04) 238-246
    PubMedGoogle Scholar
  • 43 Laitinen OM, Flo GL. Mineralization of the Supraspinatus Tendon in Dogs – A Long-Term Follow Up. J Am Anim Hosp Assoc 2000; 36: 262-267
    CrossrefPubMedGoogle Scholar
  • 44 Leighton RL. Muscle contractures in the limbs of dogs and cats. Vet Surg 1981; 10: 132-135
    CrossrefPubMedGoogle Scholar
  • 45 Lia T, Mirowitz SA. Manifestation of magic angle phenomenon: comparative study on effects of varying echo time and tendon orientation among various MR sequences. Magnetic Resonance Imaging 2003; 21: 741-744
    CrossrefPubMedGoogle Scholar
  • 46 Liehmann L, Lorinson D. Traumatic triceps tendon avulsion in a cat. J Small Anim Pract 2006; 47: 94-97
    CrossrefPubMedGoogle Scholar
  • 47 Lewis DD. et al. Gracilis or semitendinosus myopathy in 18 dogs. J Am Anim Hosp Assoc 1997; 33: 177-188
    CrossrefPubMedGoogle Scholar
  • 48 Matof K. Weitere Untersuchungen über Muskeltrichinellose erzeugt durch Aufnahme von Darmtrichinellen. Z. f. Parasitenkunde 1961; 20: 470-476
    PubMedGoogle Scholar
  • 49 May DA. et al. Abnormal signal intensity in skeletal muscle at MR imaging: patterns, pearls, and pitfalls. Radiographics 2000; 20: S295-S315
    CrossrefPubMedGoogle Scholar
  • 50 McKee WM, Macias D, May C, Scurrell EJ. Ossification of the infraspinatus tendon-bursa in 13 dogs. Vet Rec 2007; 161: 846-852
    PubMedGoogle Scholar
  • 51 McNicholas Jr. WT, Wilkens BE, Barstad RD. Luxation of the superficial digital flexor tendon in a cat. J Am Anim Hosp Assoc 2000; 36: 174-176
    CrossrefPubMedGoogle Scholar
  • 52 Mitra S. Eosinophile Myositis der extraokulären Muskeln. Ein Fallbericht. Tierärztl Prax 1998; 26 (05) 336-340
    PubMedGoogle Scholar
  • 53 Moore RW. et al. Fibrotic Myopathy of the Semitendinosus Muscle in Four Dogs. Vet Surg 1981; 10: 169-174
    CrossrefPubMedGoogle Scholar
  • 54 Napier N. et al. Muscle edema: Classification, mechanisms, and interpretation. Semin Musculoskelet Radiol 2006; 10: 258-267
    Article in Thieme ConnectPubMedGoogle Scholar
  • 55 Piercya RJ. et al. Vitamin E and exertional rhabdomyolysis during endurance sled dog racing. Neuromuscul Disord 2001; 11: 278-286
    CrossrefPubMedGoogle Scholar
  • 56 Piermattei DL, Flo GL, DeChamp CD. Diagnostic Tools (p15–24), Muscle Tendon Injuries (p226–227), Calcification of the supraspinatus tendon (p283–286), Tendosynovitis of the Biceps tendon (p286–291), Rupture of Tendon of Biceps Brachii Muscle (p291–293), Avulsion of Greater Scapular Tuberosity (p293–295), Fibrotic Contracture of Infraspinatus and Supraspinatus Muscle (p294–295), Ununited Medial Epicondyle (p352–354), Rupture of the patellar ligament (p622), Avulsion and Luxation of the proximal Tendon of Long Digital Extensor muscle (p622–626), Luxation of Tendon of Superficial Digital Flexor Muscle (p673–674), Avulsion of the Gastrocnemius Tendon (p674–677), Laceration of Calcanean/Achilles Tendon and Superficial Digital Flexor Tendon and Chronic Calcanean/Achilles Tendinitis (p677–678), Avulsion of the tibial tuberosity (639ff). In: Handbook of Small Animal Orthopedic and Fracture Repair. 4th ed. Philadelphia: Saunders Elsevier; 2006
    Google Scholar
  • 57 Platt SR, Mcconnell F, Garosi LS, Ladlow J, Stefani DE, Albert A, Shelton D. Magnetic resonance imaging in the diagnosis of canine inflammatory myopathies in three dogs. Vet Radiol Ultrasound 2006; 47 (06) 532-537
    CrossrefPubMedGoogle Scholar
  • 58 Podell M. Inflammatory myopahies. Vet Clin North Am Small Anim Pract 2002; 32 (01) 147-167
    CrossrefPubMedGoogle Scholar
  • 59 Reichel MP, Ellis JT, Dubey JP. Neosporosis and hammondiosis in dogs. J Small Anim Pract 2007; 48: 308-312
    CrossrefPubMedGoogle Scholar
  • 60 Reimers CD, Kele H, Bittermann HJ. Die Rolle bildgebender Verfahren bei neuromuskulären Erkrankungen. Dtsch Med Wsch 2000; 125: 1371-1374
    PubMedGoogle Scholar
  • 61 Rossmeisl J, Rohleder JJ. Computed tomographic features of suspected traumatic injury to the iliopsoas and pelvic limb musculature of a dog. Vet Radiol Ultrasound 2004; 45 (05) 388-392
    CrossrefPubMedGoogle Scholar
  • 62 Schultz RM, Tucker RL, Gavin PR, Bagley R, Saveraid TC, Berry CR. Magnetic resonance imaging of acquired trigeminal nerve disorders in six dogs. Vet Radiol Ultrasound 2007; 48 (02) 101-104
    CrossrefPubMedGoogle Scholar
  • 63 Seddon ML, Barry SJ. Clostridial myositis in dogs. Vet Rec 1992; 131: 84b
    PubMedGoogle Scholar
  • 64 Shelton GD. From dog to man: The broad spectrum of inflammatory myopathies. Neuromuscul Disord 2007; 17 (09) 663-670
    CrossrefPubMedGoogle Scholar
  • 65 Shelton GD. et al. Muscular dystrophy in female dogs. J Vet Intern Med 2001; 15: 240-244
    CrossrefPubMedGoogle Scholar
  • 66 Shelton GD, Cardinet GH. Pathophysiologic basis of canine muscle disorders. J Vet Intern Med 1987; 1 (01) 36-44
    CrossrefPubMedGoogle Scholar
  • 67 Stepnik MW. et al. Femoral neuropathy in a dog with iliopsoas muscle injury. Vet Surg 2006; 35: 186-190
    CrossrefPubMedGoogle Scholar
  • 68 Stuart BP, Hosa HE, Root CR. et al. Ischemic myopathy associated with systemic dirofilariasis. J Am Anim Hosp Assoc 1978; 14: 36-39
    PubMedGoogle Scholar
  • 69 Taylor C, Tangner CH. Acquired muscle contractures in the dog and cat. review of the literature and case report. Vet Comp Orthop Traumatol 2007; 20: 79-85
    Article in Thieme ConnectPubMedGoogle Scholar
  • 70 Ting D, Petersen SW, Mazzaferro EM, Worth LT, Petersen SW. Avulsion of the origin of the gastrocnemius muscle. J Am Vet Med Assoc 2006; 228 (10) 1497-1498
    CrossrefPubMedGoogle Scholar
  • 71 Toll J, Cooper B, Altschul M. Congenital myotonia in 2 domestic cats. J Vet Intern Med 1998; 12: 116-119
    CrossrefPubMedGoogle Scholar
  • 72 Unger EC, Glazer HS, Lee JKT, Ling D. MRI of Extracranial Hematomas: Preliminary Observations. Am J Roentgenol 1986; 146: 403-407
    CrossrefPubMedGoogle Scholar
  • 73 Valentine BE. et al. Fibrodysplasia ossificans progressiva in the cat. A case report. J Vet Intern Med 1992; 6: 335-340
    CrossrefPubMedGoogle Scholar
  • 74 Valentine BA, McGavin MD. Skeletal muscle. In: Pathologic Basis of Veterinary Disease. 4th ed. McGavin MD, Zachary JF. eds Philadelphia: Mosby- Elsevier; 2007: 973-1039
    Google Scholar
  • 75 Vamvakidis CD. et al. Masticatory and skeletal muscle myositis in canine leishmaniasis (Leishmania infantum). Vet Rec 2000; 146 (24) 698-703
    CrossrefPubMedGoogle Scholar
  • 76 Varela JR. et al. Complete rupture of the distal semimembranosus tendon with secondary hamstring muscles atrophy – MR findings in two cases. Skeletal Radiol 2000; 29: 362-364
    CrossrefPubMedGoogle Scholar
  • 77 Vidoni B, Hassan J, Bockstahler B, Dupre G. Kontraktur des M. gracilis – Klinik, bildgebende Diagnostik und Therapie bei einer Deutschen Schäferhündin. Wien Tierärztl Mschr 2008; 95: 8-14
    PubMedGoogle Scholar
  • 78 Vidoni B, Henninger W, Lorinson D, Mayrhofer E. Traumatic avulsion fracture of the lesser trochanter in a dog. Vet Comp Orthop Traumatol 2005; 18: 105-109
    Article in Thieme ConnectPubMedGoogle Scholar
  • 79 Williams DL. Extraocular myositis in the dog. Vet Clin North Am Small Anim Pract 2008; 38 (02) 347-359
    CrossrefPubMedGoogle Scholar
  • 80 Zandvliet MJM, Stokhof AA, Boroffka S. van den Ingh TSGAM. Intermittent Claudication in an Afghan Hound Due to Aortic Arteriosclerosis. J Vet Intern Med 2005; 19: 259-261
    CrossrefPubMedGoogle Scholar