Reestablishment of sensitivity in the latissimus dorsi transplant through anastomosis of the thoracodorsal nerve with sensitive nerves

The question as to whether anastomosis of sensory nerves is recommended for free transplants of the myocutaneous latissimus dorsi flap, reanastomosed by microvascular surgery, remains a controversial issue. In this study, a microsurgical nerve anastomosis was performed to sensitize a latissimus dorsi transplant. To determine sensation in the transplanted tissue, six patients were examined clinically. All patients had free transplants of latissimus dorsi flaps reanastomosed by microvascular surgery after tumor resection in the oral cavity. An anastomosis of the sensible auricular magnus nerve with the motor thoracodorsalis nerve was performed. Resulting sensation was determined clinically by testing for pain, temperature, pressure, two-point discrimination, and vibration. All patients showed sensation in the latissimus dorsi flap beginning between the third and the fifth month postoperatively. Therefore, resensitization of a large and voluminous myocutaneous latissimus dorsi flap should be attempted by a nerve anastomosis in this transplant.     

Dynamic reconstruction of eye closure by muscle transposition or functional muscle transplantation in facial palsy

For patients with facial palsy, lagophthalmus is often a more serious problem than the inability to smile. Dynamic reconstruction of eye closure by muscle transposition or by free functional muscle transplantation offers a good solution for regaining near-normal eye protection without the need for implants. This is the first quantitative study of three-dimensional preoperative and postoperative lid movements in patients treated for facial paralysis. Between February of 1998 and April of 2002, 44 patients were treated for facial palsy, including reconstruction of eye closure. Temporalis muscle transposition to the eye was used in 34 cases, and a regionally differentiated part of a free gracilis muscle transplant after double cross-face nerve grafting was used in 10 cases. Patients' facial movements were documented by a three-dimensional video analysis system preoperatively and 6, 12, 18, and 24 months postoperatively. For this comparative study, only the data of patients with preoperative and 12-month postoperative measurements were included. In the 27 patients with a final result after temporalis muscle transposition for eye closure, the distance between the upper and lower eyelid points during eye closing (as for sleep) was reduced from 10.33 +/- 2.43 mm (mean +/- SD) preoperatively to 5.84 +/- 4.34 mm postoperatively on the paralyzed side, compared with 0.0 +/- 0.0 mm preoperatively and postoperatively on the contralateral healthy side. In the resting position, preoperative values for the paralyzed side changed from 15.11 +/- 1.92 mm preoperatively to 13.46 +/- 1.94 mm postoperatively, compared with 12.17 +/- 2.02 mm preoperatively and 12.05 +/- 1.95 mm postoperatively on the healthy side. In the nine patients with a final result after surgery using a part of the free gracilis muscle transplant reinnervated by a zygomatic branch of the contralateral healthy side through a cross-face nerve graft, eyelid closure changed from 10.21 +/- 2.72 mm to 1.68 +/- 1.35 mm, compared with 13.70 +/- 1.56 mm to 6.63 +/- 1.51 mm preoperatively. The average closure for the healthy side was from 11.20 +/- 3.11 mm to 0.0 +/- 0.0 mm preoperatively and from 12.70 +/- 1.95 mm to 0.0 +/- 0.0 mm postoperatively. In three cases, the resting tonus of the part of the gracilis muscle transplant around the eye had increased to an extent that muscle weakening became necessary. Temporalis muscle transposition and free functional muscle transplantation for reanimation of the eye and mouth at the same time are reliable methods for reconstructing eye closure, with clinically adequate results. Detailed analysis of the resulting facial movements led to an important improvement of the authors' operative techniques within the last few years. Thus, the number of secondary operative corrections could be significantly reduced. These qualitative and quantitative studies of the reconstructed lid movements by three-dimensional video analysis support the authors' clinical concept of temporalis muscle transposition being the first-choice method in adult patients with facial palsy. In children, free muscle transplantation is preferred for eye closure, so as not to interfere with the growth of the face by transposition of a masticatory muscle. In addition, a higher degree of central plasticity in children might be expected.     

Facial animation in children with Möbius syndrome after segmental gracilis muscle transplant

M?bius syndrome is a complex congenital anomaly involving multiple cranial nerves, including the abducens (VI) and facial (II) nerves, and often associated with limb anomalies. Muscle transplantation has been used to address the lack of facial animation, lack of lower lip support, and speech difficulties these patients experience. The purpose of this study was to investigate the results of bilateral, segmental gracilis muscle transplantation to the face using the facial vessels for revascularization and the motor nerve to the masseter for reinnervation. The outcome of the two-stage procedure was assessed in 10 consecutive children with M?bius syndrome by direct interview, speech assessment, and oral commissure movement. Preoperative data were collected from direct questioning, viewing of preoperative videotapes, notes from prior medical evaluations, and rehabilitation medicine and speech pathology assessments. All of the patients developed reinnervation and muscle movement. The children who described self-esteem to be an issue preoperatively reported a significant posttransplant improvement. The muscle transplants produced a smile with an average commissure excursion of 1.37 cm. The frequency and severity of drooling and drinking difficulties decreased postoperatively in the seven symptomatic children. Speech difficulties improved in all children. Specifically, of the six children with bilabial incompetence, three received complete correction and three had significant improvement. Despite the length and complexity of these procedures, complications were minimal. Muscle transplantation had positive effects in all problematic areas, with a high degree of patient satisfaction and improvement in drooling, drinking, speech, and facial animation. The surgical technique is described in detail and the advantages over regional muscle transfers are outlined. Segmental gracilis muscle transplantation innervated by the motor nerve to the masseter is an effective method of treating patients with M?bius syndrome.     

Neurovascular free-muscle transfer for the treatment of established facial paralysis following ablative surgery in the parotid region

Neurovascular free-muscle transfer for facial reanimation was performed as a secondary reconstructive procedure for 45 patients with facial paralysis resulting from ablative surgery in the parotid region. This intervention differs from neurovascular free-muscle transfer for treatment of established facial paralysis resulting from conditions such as congenital dysfunction, unresolved Bell palsy, Hunt syndrome, or intracranial morbidity, with difficulties including selection of recipient vessels and nerves, and requirements for soft-tissue augmentation. This article describes the authors' operative procedure for neurovascular free-muscle transfer after ablative surgery in the parotid region. Gracilis muscle (n = 24) or latissimus dorsi muscle (n = 21) was used for transfer. With gracilis transfer, recipient vessels comprised the superficial temporal vessels in 12 patients and the facial vessels in 12. For latissimus dorsi transfer, recipient vessels comprised the facial vessels in 16 patients and the superior thyroid artery and superior thyroid or internal jugular vein in four. Facial vessels on the contralateral side were used with interpositional graft of radial vessels in the remaining patient with latissimus dorsi transfer. Cross-face nerve grafting was performed before muscle transfer in 22 patients undergoing gracilis transfer. In the remaining two gracilis patients, the ipsilateral facial nerve stump was used as the primary recipient nerve. Dermal fat flap overlying the gracilis muscle was used for cheek augmentation in one patient. In the other 23 patients, only the gracilis muscle was used. With latissimus dorsi transfer, the ipsilateral facial nerve stump was used as the recipient nerve in three patients, and a cross-face nerve graft was selected as the recipient nerve in six. The contralateral facial nerve was selected as the recipient nerve in 12 patients, and a thoracodorsal nerve from the latissimus dorsi muscle segment was crossed through the upper lip to the primary recipient branches. A soft-tissue flap was transferred simultaneously with the latissimus muscle segment in three patients. Contraction of grafted muscle was not observed in two patients with gracilis transfer and in three patients with latissimus dorsi transfer. In one patient with gracilis transfer and one patient with latissimus dorsi transfer, acquired muscle contraction was excessive, resulting in unnatural smile animation. The recipient nerves for both of these patients were the ipsilateral facial nerve stumps, which were dissected by opening the facial nerve canal in the mastoid process. From the standpoint of operative technique, the one-stage transfer for latissimus dorsi muscle appears superior. Namely, a combined soft-tissue flap can provide sufficient augmentation for depression of the parotid region following wide resection. A long vascular stalk of thoracodorsal vessels is also useful for anastomosis, with recipient vessels available after extensive ablation and neck dissection.     

Laparoscopic injury of the obturator nerve during fertility-sparing procedure for cervical cancer

ABSTRACT: BACKGROUND: Intraoperative injury of the obturator nerve has rarely been reported in patients with gynecological malignancies undergoing extensive radical surgeries. Irreversible damage of this nerve causes thigh paresthesia and claudication. Intraoperative repair may be done by end-to-end anastomosis or grafting when achieving tension-free anastomosis is not possible. CASE PRESENTATION: A 28-year-old woman with stage IB cervical cancer underwent fertility--sparing surgery, including conization and bilateral pelvic lymphadenectomy. The left obturator nerve was damaged intraoperatively during pelvic dissection. CONCLUSION: Immediate laparoscopic repair was successful and there was no functional deficit in the left thigh for six months postoperatively.     

Protective Effect of Oren-gedoku-to Against Induction of Neuronal Death by Transient Cerebral Ischemia in the C57BL/6 Mouse

We examined the neuroprotective effects of oren-gedoku-to (TJ15), a herbal medicine, after transient forebrain ischemia. Transient forebrain ischemia was induced by occlusion of both common carotid arteries for 15 min in C57BL/6 mice treated with TJ15. In the control ischemic group without TJ15 treatment, histologic examination of brain tissue collected seven days after reperfusion showed death of pyramidal cells in CA2-3 area of the hippocampus, unilaterally or bilaterally. In mice treated with oral TJ15 (845 mg/kg/day) for five weeks, the frequency of ischemic neuronal death was significantly lower. Immunohistochemistry for Cu/Zn-superoxide dismutase (Cu/Zn-SOD) showed strongly reactive astrocytes in the hippocampus of ischemic mice treated with TJ15. Damage to nerve cells by free radicals plays an important role in the induction of neuronal death by ischemia-reperfusion injury. Our results suggest that TJ15 protects against ischemic neuronal death by increasing the expression of Cu/Zn-SOD and suggest that oren-gedoku-to reduces the exposure of hippocampal neurons to oxidative stress.     

Differential expression of extracellular matrix and cell adhesion molecules in the olfactory nerve and glomerular layers of adult rats

Owing to the continual turnover of afferent input, the olfactory system offers a unique opportunity to study development and reorganization of neuronal networks in adults. To explore substrates that may underlie these processes in the adult olfactory system, we examined the expression and distribution of extracellular matrix and cell adhesion molecules (CAM) thought to be involved in axon guidance/extension. N-CAM, laminin, and tenascin were all detected by immunocytochemistry in the nerve and glomerular layers of the adult rat olfactory bulb, although the intensity and laminar distribution were varied. Antisera for N-CAM_total, N-CAM₁₈₀, and tenascin bound to fascicles within the olfactory nerve layer and the glomerular neuropil. However, binding was nonuniform in that only subsets of axon fascicles and restricted glomeruli showed evidence of immunoreactivity. Antilaminin and a polyclonal antitenascin similarly exhibited heterogeneous intralaminar immunoreactivity. Tenascin colocalized with glial processes at the borders of glomeruli and subcompartments of the glomerular neuropil. Laminin immunoreactivity was evident in subsets of olfactory nerve fascicles and, to a lesser extent, the glomeruli. The data are consistent with the notion that ongoing axon extension and glomerular targeting in the olfactory system is subserved in part by a heterogeneous expression of the same extracellular matrix and CAMs present at higher levels during perinatal development. © 1998 John Wiley & Sons, Inc. J Neurobiol 34: 271–282, 1998     

Management of the chest-wall deformity in male patients with Poland's syndrome

The chest-wall deformity associated with Poland's syndrome was reconstructed in eight male patients 16 to 38 years old (average age 20 years). Follow-up ranged from 1 to 10 years. Two patients had custom silicone implants placed subcutaneously. In one of these patients, the edge of the implant could be seen. Three patients had transfer of an ipsilateral pedicled latissimus dorsi muscle flap with intact thoracodorsal nerve. All these patients had noticeable atrophy of the flap, and one underwent subsequent implantation of a custom silicone implant beneath the flap. Three other patients had a custom silicone implant covered immediately by a latissimus dorsi muscle flap. All four patients who had a combination of silicone implant and latissimus dorsi muscle flap had satisfactory correction of their deformity.     

The thin latissimus dorsi perforator-based free flap for resurfacing

The authors present their experience with "thin" latissimus dorsi perforator-based free flaps for resurfacing defects. Perforator-based free flaps have been used for various kinds of reconstruction by presenting important donor structures. The thin latissimus dorsi perforatorbased free flap included only the skin and superficial adipose layer to reduce its bulkiness by dissection through the superficial fascial plane. This flap was used in 12 clinical cases, without flap necrosis or other serious postoperative complications. All of the patients were examined by preoperative power Doppler ultrasound in the spectral Doppler mode to search for the most reliable perforator. This noninvasive ultrasound technique determines the exact location and course of and ensures the reliable flow of the perforators; therefore, it greatly assists microsurgeons in saving operation time and in selecting the most suitable design for perforator flap reconstruction. We used perforators that were identified several centimeters from the lateral border of the latissimus dorsi muscle. The thin flap dimensions could be safely designed for flaps measuring up to 20 cm in length and 8 cm in width for primary closure of the donor site. Generally, a long pedicle is not required for resurfacing reconstructions, where small recipient arteries in the bed are acceptable for anastomosis with pedicles. However, pedicle dissection to the proximal vessels through the latissimus dorsi muscle was required when it was necessary to match the recipient vein for anastomosis. The authors conclude that this thin latissimus dorsi perforator-based free flap has great potential for resurfacing because of its constant thickness, easy elevation with the help of power Doppler ultrasound information, and proper flap size for moderate defects caused by scar contracture release, superficial tumor ablation, and so on.     

Breast reconstruction using the sensate latissimus dorsi musculocutaneous flap

The authors performed immediate breast reconstruction on four patients using a sensate latissimus dorsi musculocutaneous flap accompanied by neurorrhaphy during the past 6 years. In the neurorrhaphy, the lateral cutaneous branch of the dorsal primary divisions of the seventh thoracic nerve, which controls the sensation of the myocutaneous flap, was anastomosed to the lateral cutaneous branch of the fourth intercostal nerve, which controls the sensation of the breast. The subjects consisted of four patients whose postoperative follow-up period was 14 to 29 months, with an average of 19.3 months. The control subjects consisted of 10 cases with a latissimus dorsi musculocutaneous flap whose sensory nerve had not been reconstructed (postoperative follow-up period, 15 to 49 months; average, 26.9 months). The sensory examination included tests of touch, pain, and temperature. The innervated musculocutaneous flap sensation showed gradual recovery at about 6 months after surgery and reached the value of the normal side after about 1 year. In the control subjects, the recovery was gradual after more than 1 year and reached the value of the normal side in only some of the control subjects. On the basis of these findings, the authors consider the present technique to be useful for the recovery of sensation in immediate breast reconstruction.     

Role of fine needle aspiration cytology in the preoperative presumptive diagnosis of ameloblastoma

OBJECTIVE: To determine the role of fine needle aspiration cytology (FNAC) on the preoperative presumptive diagnosis of ameloblastoma. STUDY DESIGN: Sixty-three patients, diagnosed preoperatively and postoperatively with ameloblastoma, were evaluated between 1990 and 2003. The patients were classified according to whether they were diagnosed with ameloblastoma preoperatively or postoperatively, on histologic examination. RESULTS: The accuracy rate for ameloblastoma was 0.95% for all biopsy methods, while the incisional biopsy rate was 75.00%. Concerning clinical diagnosis, ameloblastoma was mistaken mostly (56.41%) for odontogenic cysts (22 of 39). CONCLUSION: FNAC should be utilized more commonly on intraosseous and soft tissue lesions in the oral and maxillofacial regions, to obtain sufficient material. It is convenient, inexpensive and noninvasive as compared with other biopsy methods.     

Neurovascular free-muscle transfer to treat facial paralysis associated with hemifacial microsomia

Despite the wide spectrum of hemifacial microsomia manifestations, treatment mainly focuses on mandible and ear abnormalities, rather than on facial paralysis. In fact, the surgical treatment of facial paralysis associated with hemifacial microsomia is quite underdeveloped, because the degree of paralysis is frequently incomplete or partial. Timing and type of surgery are also difficult to determine. Neurovascular free-muscle transfer is now a standard procedure for the dynamic smile reconstruction of longstanding facial paralysis. This type of strategy has considerable potential in the treatment of facial paralysis in patients with hemifacial microsomia. We present here our experience with neurovascular free-muscle transfer for smile reconstruction in eight patients with facial paralysis associated with hemifacial microsomia. The age of the patients at the time of surgery ranged from 7 to 28 years old, (average, 13.9 years). Six were male patients and two were female patients. The two-stage method combining gracilis muscle transfer with cross-face nerve grafting was performed in three patients, whereas the one-stage transfer of the latissimus dorsi muscle was performed in five. To construct a natural or near-natural smile, the muscles were transferred into the paralyzed cheek in all except one patient, in whom the latissimus dorsi muscle was transferred into the sublabial area to reconstruct a paralyzed lower lip. A dermal flap segment vascularized with perforating vessels from the latissimus dorsi muscle was simultaneously inserted into the underdeveloped cheek for soft-tissue augmentation in this patient. Muscle contraction was evident in all patients between 4 and 8 months after muscle transfer. Our present series revealed that neurovascular free-muscle transfer is a good option not only for smile reconstruction but also for restoration of the facial contours of patients with hemifacial microsomia. Compared with the two-stage method combining gracilis muscle transfer with cross-face nerve grafting, the one-stage method using the latissimus dorsi muscle has some advantages, including a one-stage operation, a shorter recovery period, and the absence of sequelae that occur after harvesting a sural nerve.     

Use of free thin anterolateral thigh flaps combined with cervicoplasty for reconstruction of postburn anterior cervical contractures

Free thin anterolateral thigh flaps combined with cervicoplasty were used in a series of seven patients undergoing reconstruction for previous burn injury from September of 2000 to May of 2001 at Chang Gung Memorial Hospital. This method uses a suprafascial dissection technique to provide a thin flap to improve cervical contour. Neck contractures had resulted from flame burns in six patients and from a chemical burn in one patient. The mean age was 32.7 years (range, 22 to 45 years). The size of excised scar ranged from 10 x 2 cm to 26 x 5 cm (mean, 19.7 x 3.3 cm). The size of flaps ranged from 11 x 5 cm to 26 x 8 cm (mean, 21.3 x 6.5 cm). Average operative time was 6 hours. Average hospital stay was 10 days. All flaps survived, with one flap sustaining partial marginal loss. The donor site was closed primarily in five cases and by using a split-thickness skin graft in two cases. At a mean follow-up time of 5 months, the functional improvement was measured as follows: a mean increase in extension of 30 degrees (preoperatively, 95 degrees; postoperatively, 125 degrees), a mean increase in rotation of 18 degrees (preoperatively, 59 degrees; postoperatively, 77 degrees), and a mean increase in lateral flexion of 12.5 degrees (preoperatively, 26.5 degrees; postoperatively, 39 degrees). The average cervicomandibular angle was improved by 25 degrees (preoperatively, 145 degrees; postoperatively, 120 degrees). This series demonstrates that the use of free thin anterolateral thigh flaps combined with cervicoplasty provides a one-stage reconstruction with a thin, pliable flap that achieves good cervical contour with low donor-site morbidity.     

Anatomic basis of plantar flap design: clinical applications

Closure of plantar defects with local rotation flaps was studied in 10 patients with 11 plantar defects. Ages ranged from 15 to 66 years, and the average defect was 3.0 X 3.6 cm. Two patients were diabetics. Etiology was variable and included trauma, tumors, and breakdown in patients with anesthetic plantar surfaces. Plantar flaps were designed superficial to the plantar fascia based on the proximal plantar subcutaneous plexus blood supply. Sensation was provided by including the medial calcaneal nerve territory within the flap and by performing a limited intraneural dissection of the medial and lateral plantar nerves. Flaps were medially based, although laterally based designs are also possible when sensation is absent. The follow-up period averaged 20.8 months. Patients with normal sensation preoperatively had full sensation postoperatively and were able to bear weight on the flap without limitation. There was minor breakdown in one patient with incomplete sensation. One patient developed a hematoma. Sensate plantar flaps can be designed superficial to the plantar fascia. These flaps are durable and allow normal weight-bearing on the reconstructed surface.     

Ocular motility in craniofacial reconstruction

Of 140 children undergoing major craniofacial reconstruction at The Children's Hospital of Philadelphia and examined preoperatively and postoperatively by the Ophthalmology Division, only 10 had surgically induced alteration in primary position horizontal alignment, 4 greater than 10 prism diopters. Only 2 patients had a new strabismus in primary position created by craniofacial surgery, both cranial nerve palsies. We believe early strabismus surgery is advantageous for attainment of binocularity and ease of tissue manipulation. Of 44 patients with craniofacial dysostosis (Crouzon), 20 had preoperative strabismus, and 12 required extraocular muscle surgery. Five of 12 had anomalies of extraocular muscle number and structure, usually involving the superior rectus muscle.     

Effect of glucocorticoid treatment on skin capillary blood flow and viability in cutaneous and myocutaneous flaps in the pig

The effect of methylprednisolone treatment on skin-flap viability and capillary blood flow was studied in a series of four experiments. Intramuscular methylprednisolone injections (30 mg/kg per day), given in single or divided doses preoperatively or postoperatively, had no effect in augmenting skin viability in arterialized cutaneous, myocutaneous, or random skin flaps compared with the control. Capillary blood flow was studied in arterial buttock flaps and latissimus dorsi myocutaneous flaps raised on animals treated preoperatively with methylprednisolone or saline (control), and no significant difference in capillary blood flow was noted between the treatment and control flaps. It was concluded that methylprednisolone has no significant therapeutic effect either in increasing flap viability or in increasing capillary blood flow in skin flaps in pigs.     

Immunohistochemical analysis of development of suspension and tissue neurotransplants

Engraftment and development of suspension and whole tissue allografts from the mouse brain embryonal tissue, in which cells of the green fluorescent protein (GFP) are synthesized, have been studied. The transgenic mouse cells with synthesized GFP can be used for neurotransplantation. Whole tissue and suspension transplants are able to survive more than 30 days without rejection in the brain of adult mice. It was found that the cells with synthesized GFP are able to differentiate in the neuronal and glial directions in both whole tissue and suspension transplants. The results of immunohistochemical analysis showed the reciprocal ingrowth of fibers between the cells of donor and recipient in both cases. A study of proliferation and differentiation of the cells showed the higher ability of tissue transplants for development.     

Decompression of the common peroneal nerve: experience with 20 consecutive cases

A retrospective review of 20 patients with common peroneal nerve palsy treated with decompression between 1986 and 1997 was undertaken. Subjects were evaluated preoperatively and postoperatively by electromyography, nerve conduction, and clinical measures. The mean interval between the onset of symptoms to surgery (operative delay) was 15.9 months. The mean postoperative follow-up was 32.2 months with a minimum follow-up of 1 year. Decompression was performed at the level of the fibular neck and slightly distally at the tendinous origin of the peroneus longus using a standard approach to release tight fascial structures or scar tissue. External neurolysis was performed using the operating microscope in two cases for which scarring of the nerve was identified intraoperatively. Postoperatively, 19 of 20 patients showed improvement in ankle dorsiflexion as assessed by the Medical Research Council scale. Electromyographic examination was useful in the preoperative evaluation and selection of patients for decompression surgery. In conclusion, decompression even after a 1-year delay may offer benefit and suggest early intervention in patients with a severe lesion.     

Free flaps to preserve below-knee amputation stumps: long-term evaluation

Five patients with insufficient soft-tissue coverage on below-knee amputation stumps have been treated with free-tissue transfer surgery to preserve a functional below-knee prosthetic level. The flaps employed include one latissimus dorsi myocutaneous flap, two latissimus dorsi muscle-skin graft flaps, one groin flap, and one foot-fillet flap. All five flaps survived; one patient required early venous anastomosis reexploration and revision. The patients have been followed for a mean duration of 5.5 years (range 3 to 8 years). The mean duration to first ambulation with a prosthesis was 3.6 months (range 2 to 7 months). Four of the five patients developed ulcerations on or adjacent to their flaps which required surgical revision. The patients required a mean of 1.28 prosthesis changes annually since surgery. The functional motion (mean active knee motion is 100 degrees) and ligamentous stability of the knee joints were well preserved in all patients. Five patients wear patella tendon-bearing prostheses, with one requiring an additional thigh corset. In two of the patients, nerve anastomoses to their flaps were performed. Both patients developed true cutaneous sensibility, but nevertheless experienced flap ulceration. All the patients are fully ambulatory on their free flaps. Free-tissue transfer can assist in preserving traumatic below-knee amputations so that patients can benefit from the functional advantage of a below-knee prosthetic device.     

Noninvasive detection of radiation-induced optic neuropathy by manganese-enhanced MRI

Available imaging techniques have a limited ability to detect radiation-induced injury of the normal brain. In particular, there is no noninvasive method available for detection of structural or functional neuronal damage induced by radiation. This study was designed to determine whether MRI enhanced using the neuronal track tracer MnCl(2) can detect radiation-induced optic neuropathy. A single dose of radiation (35 Gy) was delivered to produce optic neuropathy in Fischer 344 rats by using a stereotactic method with a 6-mm dorsoventral secondary collimator. At 6 months after irradiation, MRI was performed in 1-mm sections using a 7-T magnetic field with the neuronal tracer MnCl(2) injected into the vitreous of the eye 24 h prior to imaging. The rats were then killed humanely for a histological study with hematoxylin and eosin, glial fibrillary acidic protein (Gfap) for the detection of astrocytic activity, Luxol Fast Blue/Periodic Acid Schiff (LFB/PAS) for the detection of myelinization status, and Bielschowski silver stain for axon status. In nonirradiated control animals, T1-weighted MRI with manganese vitreous injection revealed an optic nerve track that was brightly enhanced from the orbit to the optic chiasm. In the irradiated animals, there was clear evidence of the damage at the optic chiasm and optic nerves, with loss of axon and demyelinization within the site of irradiation upon histological examination. T1-weighted MRI with manganese vitreous injection showed an enhancing optic nerve posterior to the orbit. However, this enhancement disappeared at the site of irradiation. The area of loss of manganese contrast on the MRI scan correlated well with the area of histological abnormality showing axonal degeneration and demyelinization. Radiation-induced optic neuropathy was thus detected noninvasively by MRI with the antegrade neuronal tracer manganese, which exhibited negative contrast enhancement by causing loss of signal. This study represents the first demonstration of MR imaging of radiation-induced neuronal damage and could provide a means to explore the biological and functional integrity of neuronal pathways.