BACKGROUND

1. Field

Embodiments of the present invention relate to diagnostic imaging. More particularly, embodiments of the present invention relate to a method to diagnose and characterize lesions in a peripheral nervous system.

2. Discussion of Related Art

Currently, in the setting of acute injury, there exists no method to reliably distinguish peripheral nerve injuries that will spontaneously resolve from those that will require surgical intervention to restore function. U.S. Pat. No. 5,059,415 to Neuwelt titled Method Of Diagnostically Imaging Lesions In The Brain Inside A Blood-Brain Barrier is incorporated by reference in its entirety. In some cases, the decision for surgery is made only after an observation period that can last several months. Early intervention translates to better functional outcomes.

Additionally, functional outcomes hinge on the ability of the regenerating nerve to reach its muscular target before motor end-plate demise. This irreversible denervation of the muscle occurs at approximately eighteen months. If diagnosis could be made immediately, surgical intervention could take place sooner; thereby increasing the likelihood the regenerating nerve will reach its target sooner, e.g., before eighteen months elapse. The length of time that elapses from time of injury to surgery is inversely proportional to the degree of functional recovery.

Accordingly, there is a need to provide a method for early identification and characterization of peripheral nerve injuries that will require surgical intervention to revolutionize the surgical management of peripheral nerve injuries.

(The following references are incorporated by reference in their entireties: Sunderland S. The anatomy and physiology of nerve injury. Muscle Nerve 1990; 13:771-84.) (Lee D K, Wolfe S W. Peripheral nerve injury and repair. J Am Acad Orthop Surg. 2000; 8(4):243-52.) (Johns R, Boppart S A. Magnetomotive molecular nanoprobes. Curr Med Chem. 2011; 18(14):2103-14.) (Luchetti A, Milani D, Ruffini F, Galli R, Falini A, Quattrini A, Scotti G, Comi G, Martino G, Furlan R, Politi L S. Monoclonal Antibodies Conjugated with Superparamagnetic Iron Oxide Particles Allow Magnetic Resonance Imaging Detection of Lymphocytes in the Mouse Brain. Mole Imagaing. 2011 Sep. 28.) (Birch R. Chapter 32—Nerve Repair. In, Wolfe S W, Hotchkiss R N, Pedereson W C, Kozin S H. Green's Operative Hand Surgery 6thEd., Elsevier, 2011.) (Spinner R J, Shin A Y, Hert-Blouin M N, Elhassan B T, Bishop A T. Chapter 38—Traumatic Brachial Plexus Injury. In, Wolfe S W, Hotchkiss R N, Pedereson W C, Kozin S H. Green's Operative Hand Surgery 6thEd., Elsevier, 2011.) (Waters, P M. Chapter 44—Pediatric Brachial Plexus Palsy. In, Wolfe S W, Hotchkiss R N, Pedereson W C, Kozin S H. Green's Operative Hand Surgery 6thEd., Elsevier, 2011.) (Neumaier C E, Baio G, Ferrini S, Corte G, Daga A. MR and iron magnetic nanoparticles. Imaging opportunities in preclinical and translational research. Tumori. 2008; 94:226-233.) (Mohler L R, Hanel D P. Closed Fractures Complicated by Peripheral Nerve Injury. J Am Acad Orthop Surg 2006; 14:32-37.) (Weerasuriya A, Mizisin A P. Chapter 6—The Blood-Nerve Barrier: Structure and Functional Significance. In, Sukriti N (ed.), The Blood-Brain and Other Neural Barriers: Reviews and Protocols, Methods in Molecular Biology, vol 686, Springer Science 2011.) (Wessig C. Chapter 12—Detection of Blood-Nerve Barrier Permeability by Magnetic Resonance Imaging. In, Sukriti N (ed.), The Blood-Brain and Other Neural Barriers: Reviews and Protocols, Methods in Molecular Biology, vol 686, Springer Science 2011.) (Grant G A, Goodkin R, Maravilla K R, Kliot M. MR Neurography: diagnostic utility in the surgical treatment of peripheral nerve disorders. Neuroimg Clin N Am 2004; 14:115-133.) Ecklund J M, Ling G S. From the battlefront: peripheral nerve surgery in modern day warfare. NeruosurgClin N Am. 2009 January; 20(1):107-110.vii. Review, and Kretschemer T, Heinen C W, Antonaiadis G, Richter H P, Konig R W. latrogenic nerve injuries. Neurosurg Clin N Am. 2009 Jan. 20(1):73-90, vii. Review, and Kozin S H. The evaluation and treatment of children with brachial plexus birth palsy. J Hand Surg Am. 2011 August; 36(8):1360-1369.)

SUMMARY

The following brief description is provided to indicate the nature of the subject matter disclosed herein. While certain aspects of the present inventive concept are described below, the summary is not intended to limit the scope of the present inventive concept. Embodiments of the present inventive concept provide a diagnostic imaging method. The present inventive concept does not suffer from and remedies the deficiencies of conventional methods such as those previously set forth herein.

The present inventive concept provides, in its simplest form, an improved method for diagnosing and characterizing peripheral nerve lesions to permit early identification and characterization of peripheral nerve injuries that will require surgical intervention.

The method provided by the present general inventive concept is advantageous over conventional methods for at least the reason that the method enables the accurate analysis of peripheral nerve lesions and the ability to distinguish lesions where the blood-nerve barrier (“BNB”) remains intact, and therefore has greater self-regeneration potential from lesions where the connective tissue layers comprising the BNB are disrupted, and therefore require surgical intervention to obtain any meaningful neurological recovery. The present method represents an advance in the art of diagnosis of peripheral nerve lesions.

The aforementioned may be achieved in one aspect of the present invention by providing a method to diagnose and/or characterize peripheral nerve lesions. The method may include the step of introducing a chemical agent operable to bind directly to peripheral nerve lesions in which the blood-nerve barrier is compromised such that a target molecule is immune privileged and unavailable for interaction with the chemical agent unless the blood-nerve barrier is compromised. The target molecule is such that it is (i) not shielded in injured nerves or abnormal tissue via the blood-nerve barrier and/or (ii) shielded in uninjured nerves or normal tissue via the blood-nerve barrier. The target molecule is immune privileged and/or unavailable for interaction with the chemical agent unless the blood-nerve barrier is compromised. The method may also include the step of attaching a label to the chemical agent. The chemical agent with the label may be operable to localize in regions where a peripheral of the nerve-blood barrier is disrupted.

The method may also include the step of quantitatively analyzing the peripheral nerve or nerves to determine the amount of labeling agent present. The analyzing may be performed using magnetic resonance imaging techniques or the like. The chemical agent may be a monoclonal antibody. The chemical agent may also be operable to bind specifically and exclusively to the peripheral nerve lesions in which the blood-nerve barrier is compromised. The chemical agent that will localize at peripheral nerve lesions in which the blood-nerve barrier is compromised may be an antibody against an axonal protein.

The blood-nerve barrier may be compromised by neurotmesis. The label attached to the chemical may be gadolinium-DTPA or superparamagnetic iron oxide nanoparticles. The method may enable the accurate analysis of peripheral nerve lesions and the ability to distinguish axonotmetic lesions with greater self-regeneration potential from neurotmetic lesions that may require intervention.

Additional aspects, advantages, and utilities of the present inventive concept will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the present inventive concept.

