Aaron G. Filler

Magnetic resonance neurography of peripheral nerve lesions in the lower extremity

OBJECTIVE We describe the clinical application and utility of high-resolution magnetic resonance neurography (MRN) techniques to image the normal fascicular structure of peripheral nerves and its distortion by mass lesions or trauma in the lower extremity. METHODS MRN images were obtained using a standard 1.5 Tesla magnet and custom built phased-array coils. Patients were imaged using T1-weighted spin echo without and with gadolinium, T2-weighted fast spin echo with fat peripheral nerve tumors (three neurofibromas and one schwannoma), two with intraneural cysts, and three with traumatic peripheral nerve lesions. Six patients with peripheral nerve mass lesions underwent surgery, thereby allowing MRN images to be correlated with intraoperative and pathological findings. RESULTS Preoperative MRN accurately imaged the normal fascicular anatomy of peripheral nerves and precisely depicted its relation to tumor and cystic lesions. Increased signal on T2-weighted fast spin-echo and short tau inversion recovery fast spin-echo pulse sequences was seen in the peripheral nerve fascicles of patients with clinical and electrodiagnostic evidence of nerve injury. CONCLUSION MRN proved useful in the preoperative evaluation and planning of surgery in patients with peripheral nerve lesions.

Magnetic resonance neurography of peripheral nerve degeneration and regeneration

1To date, no study has shown that this technique can visualise the process of peripheral nerve degeneration and regeneration over time. We show how MRN signal changes during degeneration and regeneration of an injured peripheral nerve correlated with clinical and electrodiagnostic findings. A 29-year-old man had a traumatic laceration of the right sciatic nerve in the lower thigh resulting in an inability to dorsiflex and evert his right foot. Emergency surgery documented complete transection of the peroneal nerve which was surgically anastomosed. On referral 2 months later, clinical and electrodiagnostic examinations confirmed complete denervation of all muscles supplied by this nerve. Follow-up examinations 4 and 6 months after the injury showed no reinnervation of these muscles. MRN images were obtained on a 1·5-Tesla scanner (Signa; General Electric, Milwaukee, WI) with custom-designed phasedarray coils and imaging protocols previously described: 1

Magnetic resonance neurography and diffusion tensor imaging: origins, history, and clinical impact of the first 50,000 cases with an assessment of efficacy and utility in a prospective 5000-patient study group.

OBJECTIVEMethods were invented that made it possible to image peripheral nerves in the body and to image neural tracts in the brain. The history, physical basis, and dyadic tensor concept underlying the methods are reviewed. Over a 15-year period, these techniques—magnetic resonance neurography (MRN) and diffusion tensor imaging—were deployed in the clinical and research community in more than 2500 published research reports and applied to approximately 50 000 patients. Within this group, approximately 5000 patients having MRN were carefully tracked on a prospective basis. METHODSA uniform Neurography imaging methodology was applied in the study group, and all images were reviewed and registered by referral source, clinical indication, efficacy of imaging, and quality. Various classes of image findings were identified and subjected to a variety of small targeted prospective outcome studies. Those findings demonstrated to be clinically significant were then tracked in the larger clinical volume data set. RESULTSMRN demonstrates mechanical distortion of nerves, hyperintensity consistent with nerve irritation, nerve swelling, discontinuity, relations of nerves to masses, and image features revealing distortion of nerves at entrapment points. These findings are often clinically relevant and warrant full consideration in the diagnostic process. They result in specific pathological diagnoses that are comparable to electrodiagnostic testing in clinical efficacy. A review of clinical outcome studies with diffusion tensor imaging also shows convincing utility. CONCLUSIONMRN and diffusion tensor imaging neural tract imaging have been validated as indispensable clinical diagnostic methods that provide reliable anatomic pathological information. There is no alternative diagnostic method in many situations. With the elapsing of 15 years, tens of thousands of imaging studies, and thousands of publications, these methods should no longer be considered experimental.OBJECTIVE Methods were invented that made it possible to image peripheral nerves in the body and to image neural tracts in the brain. The history, physical basis, and dyadic tensor concept underlying the methods are reviewed. Over a 15-year period, these techniques-magnetic resonance neurography (MRN) and diffusion tensor imaging-were deployed in the clinical and research community in more than 2500 published research reports and applied to approximately 50,000 patients. Within this group, approximately 5000 patients having MRN were carefully tracked on a prospective basis. METHODS A uniform Neurography imaging methodology was applied in the study group, and all images were reviewed and registered by referral source, clinical indication, efficacy of imaging, and quality. Various classes of image findings were identified and subjected to a variety of small targeted prospective outcome studies. Those findings demonstrated to be clinically significant were then tracked in the larger clinical volume data set. RESULTS MRN demonstrates mechanical distortion of nerves, hyperintensity consistent with nerve irritation, nerve swelling, discontinuity, relations of nerves to masses, and image features revealing distortion of nerves at entrapment points. These findings are often clinically relevant and warrant full consideration in the diagnostic process. They result in specific pathological diagnoses that are comparable to electrodiagnostic testing in clinical efficacy. A review of clinical outcome studies with diffusion tensor imaging also shows convincing utility. CONCLUSION MRN and diffusion tensor imaging neural tract imaging have been validated as indispensable clinical diagnostic methods that provide reliable anatomic pathological information. There is no alternative diagnostic method in many situations. With the elapsing of 15 years, tens of thousands of imaging studies, and thousands of publications, these methods should no longer be considered experimental.

Diagnosis and treatment of pudendal nerve entrapment syndrome subtypes: imaging, injections, and minimal access surgery

OBJECT To improve diagnostic accuracy and achieve high levels of treatment success in patients with pudendal nerve entrapment (PNE) syndromes, the author of this study applied advanced technology diagnostics in distinguishing the various syndrome types according to the different entrapment locations and evaluated new minimal access surgical techniques to treat each subtype. METHODS Two hundred cases were prospectively evaluated using a standardized set of patient-completed functional and symptom assessments, a collection of new physical examination maneuvers, MR neurography, open MR image-guided injections, intraoperative neurophysiology, minimal access surgery, and formal outcome assessment with the Oswestry Disability Index, pain diagrams, and analog pain scales. RESULTS Four primary types of PNE syndromes were identified based on the different locations of entrapment: Type I, entrapment at the exit of the greater sciatic notch in concert with piriformis muscle spasm; Type II, entrapment at the level of the ischial spine, sacrotuberous ligament, and lesser sciatic notch entrance; Type III, entrapment in association with obturator internus muscle spasm at the entrance of the Alcock canal; and Type IV, distal entrapment of terminal branches. The application of new, targeted minimal access surgical techniques led to sustained good to excellent outcomes (50-100% improvement in the pain score or functional score) in 87% of patients. Most of these patients obtained most of their improvement within 4 weeks of surgery, although some continued to experience progressive improvements up to 12 months after surgery. CONCLUSIONS The application of advanced diagnostics to categorize PNE syndrome origins into 4 major subtypes and the subsequent treatment of each subtype with a tailored strategy greatly improved therapeutic outcomes as compared with those reported when only a single treatment paradigm was applied to all patients.

The History, Development and Impact of Computed Imaging in Neurological Diagnosis and Neurosurgery: CT, MRI, and DTI

A steady series of advances in physics, mathematics, computers and clinical imaging science have progressively transformed diagnosis and treatment of neurological and neurosurgical disorders in the 115 years between the discovery of the X-ray and the advent of high resolution diffusion based functional MRI. The story of the progress in human terms, with its battles for priorities, forgotten advances, competing claims, public battles for Nobel Prizes, and patent priority litigations bring alive the human drama of this remarkable collective achievement in computed medical imaging.

Magnetic Resonance Neurography for Cervical Radiculopathy: A Preliminary Report

Magnetic resonance neurography was used to directly image cervical spinal nerves in patients with clinical and radiographic evidence of cervical radiculopathy. A magnetic resonance imaging phased-array coil system was used to obtain high-resolution coronal T1-weighted spin echo, coronal/axial T2-weighted fast spin echo with fat saturation, and coronal/axial fast short tau inversion recovery weighted images of the cervical spine and spinal nerves. Three patients with neck and upper extremity pain and one asymptomatic volunteer were studied. The T2-weighted and the fast short tau inversion recovery images demonstrated markedly increased signal in the proximal portion of the affected spinal nerves. In two patients, contrast-to-noise measurements of the affected spinal nerves showed a markedly increased intensity compared with that of the noninvolved spinal nerves. Our findings demonstrate that phased-array coils used in conjunction with magnetic resonance neurography sequences can detect signal abnormalities within compressed cervical spinal nerves in patients with corresponding radicular symptoms and findings. This technique may prove to be helpful in evaluating patients with multilevel disc and/or spondylotic disease of the cervical spine.

Emergence and optimization of upright posture among hominiform hominoids and the evolutionary pathophysiology of back pain.

The lordotic region of the lumbar spine is a significant focus of pain and dysfunction in the human body, and its susceptibility to disorders may reflect its substantial reconfiguration during the course of human evolution. The basic anatomy of the lumbar vertebra in Old World Monkeys and Early Miocene apes, or proconsulids, retains typical mammalian architecture. The lumbar vertebra in humans is different in the repositioning of the lumbar transverse process dorsal to the vertebral body rather than originating on the body itself and in the loss of the styloid process that is adjacent to the facets in other primates. These two features appeared in Morotopithecus bishopi 21.6 million years ago, suggesting that this ape is the founder of an upright hominiform lineage. The iliocostalis lumborum muscles migrated onto the iliac crest approximately 18 million years ago, becoming a powerful lateral flexor muscle of the trunk. The posterior superior iliac spine shifted far dorsal to the longissimus insertion in the genus Homo between 1 and 2 million years ago, making this muscle a powerful extensor of the lumbar spine. Functionally, the establishment of strong muscular flexors and extensors adds dynamic compressive stresses to the lumbar disks and also makes these muscles susceptible to strain.

Tri-partite complex for axonal transport drug delivery achieves pharmacological effect.

BackgroundTargeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System) neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy and limit clinical utility for many classes of pharmaceuticals. Axonal transport from the periphery offers a possible selective route, but there has been little progress towards design of agents that can accomplish targeted delivery via this intraneural route. To achieve this goal, we developed a tripartite molecular construction concept involving an axonal transport facilitator molecule, a polymer linker, and a large number of drug molecules conjugated to the linker, then sought to evaluate its neurobiology and pharmacological behavior.ResultsWe developed chemical synthesis methodologies for assembling these tripartite complexes using a variety of axonal transport facilitators including nerve growth factor, wheat germ agglutinin, and synthetic facilitators derived from phage display work. Loading of up to 100 drug molecules per complex was achieved. Conjugation methods were used that allowed the drugs to be released in active form inside the cell body after transport. Intramuscular and intradermal injection proved effective for introducing pharmacologically effective doses into selected populations of CNS neurons. Pharmacological efficacy with gabapentin in a paw withdrawal latency model revealed a ten fold increase in half life and a 300 fold decrease in necessary dose relative to systemic administration for gabapentin when the drug was delivered by axonal transport using the tripartite vehicle.ConclusionSpecific targeting of selected subpopulations of CNS neurons for drug delivery by axonal transport holds great promise. The data shown here provide a basic framework for the intraneural pharmacology of this tripartite complex. The pharmacologically efficacious drug delivery demonstrated here verify the fundamental feasibility of using axonal transport for targeted drug delivery.

Minimal access nerve surgery and interventional magnetic resonance imaging.

OBJECTIVEDevelop and assess the utility of novel minimal access techniques including percutaneous open-configuration interventional magnetic resonance imaging (iMRI), open surgery using open or closed/cylindrical iMRI systems, and minimal access open surgery with electromyographic guidance in a standard operating room. METHODSFor more than 2500 percutaneous open iMRI procedures, 25 incisional surgery open iMRI cases, 3 incisional surgery closed/cylindrical iMRI cases, 25 computed tomography–guided percutaneous procedures, and more than 1000 minimal access incisional surgery cases in the standard operating room with electromyographic guidance, cycle time for intraoperative data collection and numbers of guidance events per case were assessed. RESULTSCycle time varied greatly. The minimum was for open surgery in the standard operating room with direct nerve stimulation for electromyography, requiring 10 to 15 seconds, which was applicable for dozens of assessments during the surgery and had negligible effects on total surgical time. Percutaneous procedures in the open iMRI environment allowed for 20 or 30 imaging events during a procedure, with cycle times of between 10 and 20 seconds. Incisional surgery in the open iMRI system had a cycle time of about 1 to 5 minutes for “in-magnet” procedures and about 5 to 10 minutes for “magnet-adjacent” procedures. Incisional surgery in closed/cylindrical iMRI procedures had a cycle time of 45 to 60 minutes, and the technique proved awkward to use more than once or twice per surgical case. CONCLUSIONPercutaneous open-configuration iMRI provides clear benefits over computed tomography or ultrasound. Minimal access surgery and incisional open-configuration iMRI are useful and effective in some situations. Closed/cylindrical iMRI systems pose challenges for patient safety, add greatly to surgical time, and provide limited useful intraoperative benefits.