Kenji Ohata

Diagnostic Accuracy of 11C-Methionine PET for Differentiation of Recurrent Brain Tumors from Radiation Necrosis After Radiotherapy

We evaluated the diagnostic accuracy of PET with l-methyl-11C-methionine (11C-MET) for the differentiation of recurrent brain tumors from radiation necrosis. Methods: Seventy-seven patients who had been previously treated with radiotherapy after primary treatment for metastatic brain tumor (n = 51) or glioma (n = 26) were studied to clarify the diagnostic performance of 11C-MET PET in differentiating between recurrent brain tumors and radiation necrosis. A total of 88 PET scans with 11C-MET were obtained; sometimes more than one scan was obtained when there was an indication of recurrent brain tumor or radiation necrosis. A definitive diagnosis was made on the basis of pathologic examination for recurrent brain tumors and on the basis of pathologic examination or clinical course for radiation necrosis. Several indices characterizing the lesions were determined; these included mean and maximum standardized uptake values (SUVmean and SUVmax, respectively) and the ratios of lesion uptake to contralateral normal frontal-lobe gray matter uptake corresponding to the SUVmean and the SUVmax (L/Nmean and L/Nmax, respectively). Receiver-operating-characteristic (ROC) curve analysis was used to determine the optimal index of 11C-MET PET and cutoff values for the differential diagnosis of tumor recurrence and radiation necrosis. Results: The values of each index of 11C-MET PET tended to be higher for tumor recurrence than for radiation necrosis. There were significant differences between tumor recurrence and radiation necrosis in all of the indices except for the L/Nmax for glioma. ROC analysis indicated that the L/Nmean was the most informative index for differentiating between tumor recurrence and radiation necrosis. An L/Nmean of greater than 1.41 provided the best sensitivity and specificity for metastatic brain tumor (79% and 75%, respectively), and an L/Nmean of greater than 1.58 provided the best sensitivity and specificity for glioma (75% and 75%, respectively). Conclusion: 11C-MET PET can provide quantitative values to aid in the differentiation of tumor recurrence from radiation necrosis, although these values do not appear to be absolute indicators. Quantitative analysis of 11C-MET PET data may be helpful in managing irradiated brain tumors.

Methionine positron emission tomography for differentiation of recurrent brain tumor and radiation necrosis after stereotactic radiosurgery--in malignant glioma.

ObjectFollowing stereotactic radiosurgery (SRS), we examined how to differentiate radiation necrosis from recurrent malignant glioma using positron emission tomography (PET) with11C-methionine (Met).MethodsMet-PET scans were obtained from 11 adult cases of recurrent malignant glioma or radiation injury, suspected on the basis of magnetic resonance images (MRI). Patients had previously been treated with SRS after primary treatment. PET images were obtained as a static scan of 10 minutes performed 20 minutes after injection of Met. We defined two visual grades (e.g., positive or negative Met accumulation). On Met-PET scans, the portion of the tumor with the highest accumulation was selected as the region of interest (ROI), tumor-versus-normal ratio (TN) was defined as the ratio of average radioisotope counts per pixel in the tumor (T), divided by average counts per pixel in normal gray matter (N). The standardized uptake value (SUV) was calculated over the same tumor ROI. Met-PET scan accuracy was evaluated by correlating findings with subsequent histological analysis (8 cases) or, in cases without surgery or biopsy, by the subsequent clinical course and MR findings (3 cases).ResultsHistological examinations in 8 cases showed viable glioma cells with necrosis in 6 cases, and necrosis without viable tumor cells in 2 cases. Three other cases were considered to have radiation necrosis because they exhibited stable neurological symptoms with no sign of massive enlargement of the lesion on follow-up MR after 5 months. Mean TN was 1.31 in the radiation necrosis group (5 cases) and 1.87 in the tumor recurrence group (6 cases). Mean SUV was 1.81 in the necrosis group and 2.44 in the recurrence group. There were no statistically significant differences between the recurrence and necrosis groups in TN or SUV. Furthermore, we made a 2 x 2 factorial cross table (accumulation or no accumulation, recurrence or necrosis). From this result, the Met-PET sensitivity, specificity, and accuracy in detecting tumor recurrence were determined to be 100%, 60%, and 82% respectively. In a false positive-case, glial fibrillary acidic protein (GFAP) immunostaining showed a positive finding.ConclusionThere were no significant differences between recurrent malignant glioma and radiation necrosis following SRS in Met-PET. However, this study shows Met-PET has a sensitivity and accuracy for differentiating between recurrent glioma and necrosis, and presents important information for developing treatment strategies against post radiation reactions.

Comparison of neuropsychological outcomes after selective amygdalohippocampectomy versus anterior temporal lobectomy

Transsylvian selective amygdalohippocampectomy (TSA) is an operative technique designed to spare unaffected brain tissue during surgical treatment for mesial temporal lobe epilepsy. In contrast to standard anterior temporal lobectomy (ATL), the advantages of TSA with respect to postoperative cognitive outcome are equivocal. We compared cognitive function before and after surgery in 49 patients with unilateral mesial temporal lobe seizures who underwent either ATL (n=17) or TSA (n=32). All patients received neuropsychological testing before and 1 year after surgery. The intelligence quotient (IQ) increased postoperatively in both surgical groups. Memory evaluation in the ATL group revealed a postoperative decline in nonverbal memory after right-sided resection and a postoperative decline in verbal memory after left-sided resection. In the TSA group, there was a slight postoperative decline only in verbal memory after left-sided resection, but other memory function was well preserved. In particular, there was significant postoperative improvement in verbal memory after right-sided resection. Overall, memory function was better preserved in the TSA group than in the ATL group.

Evaluation of treatment effects in brain abscess with positron emission tomography: comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine.

Positron emission tomography (PET) imaging is in common use preoperatively to clinically evaluate patients who present with central nervous system mass lesions. The usefulness of PET is also recognized as a method to detect intracranial tumorous lesions. A number of papers report that some inflammatory processes also showed the uptake of Fluorine-18-Fluorodeoxyglucose (FDG) and Carbon-11-Methionine (Met) tracers. We performed two PET studies before and after treatment in 4 patients with brain abscess. PET showed the uptake of both tracers to the brain abscess before treatment. The area showing an increased uptake of Met corresponded closely to the enhanced area on both CT and MR images. FDG-PET visually showed an uptake of FDG in a small area corresponding to an enhanced lesion within the CT and MR images. After treatment the area of lesions became small on enhancement CT or MRI and both PET studies showed reduced lesion and decreased uptake. The mechanism of Met uptake in the inflammatory area may be related to the higher metabolic rate and the active transport of amino acids as well as disruption of the blood brain barrier. Furthermore, it appears that the mechanism of FDG uptake is also related to a higher metabolic rate and, in addition, is related to the increased density of inflammatory cells. PET studies, more directly, reflect the degree of inflammatory response in brain abscess than enhancement CT or MRI. Therefore, PET is useful in detecting the inflammatory lesion and assessing the clinical effects of antibiotics treatment on brain abscesses.

Surgical outcome of intramedullary spinal cord ependymoma.

Summary Surgical outcome of intramedullary spinal cord ependymoma was investigated in order to define the treatment strategy. We have operated on 18 cases of intramedullary spinal cord ependymoma based on the principle of radical resection. The follow-up periods ranged from 10 months to 249 months with an average of 86.2 months. Postoperative neurological status in the long follow-up periods was compared to the pre-operative status and was correlated with the histological grade of malignancy. Total removal of the tumour was achieved in 17 cases, and subtotal removal followed by radiation therapy was conducted in 1 case. There was neither surgical mortality nor radiological evidence of recurrence in the long-term follow-up periods. The final outcome of the neurological condition was improved in 1 case, unchanged in 15 cases (including a case of subtotal removal) and deteriorated in 2 cases. The deterioration was in the form of gait disturbance due to the worsening of proprioception in 2 cases and dysaethesia in 1 case. Histological examination showed no evidence of anaplasia in 6 cases, evidence of early anaplasia in 10 cases, and moderate evidence of anaplasia in 2 cases. No relationship between the histological malignancy and clinical course was found. Intramedullary spinal cord ependymoma should be removed radically as early as possible while taking great care to avoid posterior column injury. Histologically malignant ependymoma might be a clinical exception.

The role of radical microsurgical resection in multimodal treatment for skull base meningioma.

OBJECT Because resection followed by timely stereotactic radiosurgery (SRS) is becoming a standard strategy for skull base meningiomas, the role of initial surgical tumor reduction in this combined treatment should be clarified. METHODS This study examined 161 patients with benign skull base meningiomas surgically treated at Osaka City University between January 1985 and December 2005. The mean follow-up period was 95.3 months. Patients were categorized into 3 groups based on the operative period and into 4 groups based on tumor location. Maximal resection was performed as first therapy throughout all periods. In the early period (1985-1994), in the absence of SRS, total excision of the tumor was intentionally performed for surgical cure of the disease. In the mid and late periods (1995-2000 and 2001-2005), small parts of the tumor invading critical neurovascular structures were left untouched to obtain good functional results. Residual tumors with high proliferation potential (Ki 67 index > 4%) or with progressive tendencies were treated with SRS. The extent of initial tumor resection, recurrence rate, Karnofsky Performance Scale score, and complication rate were investigated in each group. RESULTS The mean tumor equivalent diameter of residual tumors was 3.67 mm in the no-recurrence group and 11.7 mm in the recurrence group. The mean tumor resection rate (TRR) was 98.5% in the no-recurrence group and 90.1% in the recurrence group. A significant relationship was seen between postoperative tumor size, TRR, and recurrence rate (p < 0.001), but the recurrence rate showed no significant relationship with any other factors such as operative period (p = 0.48), tumor location (p = 0.76), or preoperative tumor size (p = 0.067). The mean TRR was maintained throughout all operative periods, but the complication rate was lowest and postoperative Karnofsky Performance Scale score was best in the late period (p < 0.001 each). Late-period results were as follows: mean TRR, 97.9%; mortality rate, 0%; and severe morbidity rate, 0%. Stereotactic radiosurgery procedures were added in 27 cases (16.8%) across all periods. Throughout all follow-up periods, 158 tumors were satisfactorily controlled by maximal possible excision alone or in combination with adequate SRS. CONCLUSIONS The combination of maximal possible resection and additional SRS improves functional outcomes in patients with skull base meningioma. A TRR greater than 97% in volume can be achieved with satisfactory functional preservation and will lead to excellent tumor control in combined treatment of skull base meningioma.

Assessment of cervical spondylotic myelopathy using diffusion tensor magnetic resonance imaging parameter at 3.0 tesla.

Study Design. Cross-sectional study. Objective. To assess spinal cord condition in patients with cervical spondylosis (CS), using diffusion tensor imaging parameter. Summary of Background Data. Although myelopathy is a common symptom after CS, clinically objective assessment for determination of surgical intervention is not straightforward. Methods. Twenty-six patients with CS and 30 normal control subjects were enrolled. Diffusion tensor imaging was obtained using a single-shot fast spin-echo–based sequence at 3.0 T. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in the axial plane at 6 spinal levels. To evaluate MD and FA in patients with CS considering the normal variation at each spinal level and between spinal levels, MD and FA at the most compressed spinal level were transformed to normalized values with a z score. Presence of myelopathy was predicted with the MD and FA z scores. Diagnostic validity of MD and FA was compared with receiver operating characteristic analysis. More effective parameter and the optimal cutoff value for prediction were determined. Results. In normal subjects, MD and FA were significantly different between spinal levels. In patients with myelopathy, an MD increase or an FA decrease was demonstrated in most cases. Although both an MD increase and an FA decrease had diagnostic validity for myelopathy, receiver operating characteristic analysis demonstrated a higher sensitivity and specificity for prediction of an MD increase than an FA decrease (areas under the curve for MD and FA were 0.903 and 0.760, respectively). An MD z score of 1.40 was considered to be the best diagnostic cutoff value with 100% sensitivity and 75% specificity. Conclusion. Myelopathy can be predicted with high accuracy with diffusion tensor imaging parameter, with the MD z score at the most compressed spinal level. Level of Evidence: 3

Memory outcome following transsylvian selective amygdalohippocampectomy in 62 patients with hippocampal sclerosis

OBJECT It remains unclear whether selective amygdalohippocampectomy, an operative technique developed for use in epilepsy surgery to spare unaffected brain tissue and thus minimize the cognitive consequences of temporal lobe surgery, actually leads to a better memory outcome. The present study was performed to determine the effects of selective surgery on memory outcome in patients with intractable mesial temporal lobe epilepsy due to hippocampal sclerosis treated using transsylvian selective amygdalohippocampectomy (TSA). METHODS The study population consisted of 62 patients with left hemisphere language dominance who underwent left-(31 patients) or right-sided (31 patients) TSA. All patients underwent comprehensive neuropsychological testing before and 1 month and 1 year after unilateral TSA. Verbal Memory I, Nonverbal Memory I, Total Memory, Attention, and Delayed Recall were assessed using the Wechsler Memory Scale-Revised, whereas Verbal Memory II was assessed using the Miyake Verbal Retention Test (MVRT), and Nonverbal Memory II was assessed using the Benton Visual Retention Test. Separate repeated-measures multivariate analysis of variance (MANOVA) were performed for these intervals with memory scores. RESULTS The results of MANOVA indicated that patients who underwent right-sided TSA showed significant improvements in Verbal Memory I (preoperatively vs 1 month postoperatively, p < 0.0001; and preoperatively vs 1 year postoperatively, p = 0.0002), Nonverbal Memory I (preoperatively vs 1 month postoperatively, p = 0.0003; and preoperatively vs 1 year postoperatively, p = 0.006), and Delayed Recall (preoperatively vs 1 month postoperatively, p = 0.028) at both 1-month and 1-year follow-ups. In addition, Verbal Memory II (MVRT) was also significantly improved 1 year after surgery (p = 0.001). In the group of patients who underwent left-sided TSA, both Verbal Memory I and II were maintained at the same level 1 month after surgery, whereas the Verbal Memory I score 1 year after surgery increased with marginal significance (p = 0.074). In addition, Verbal Memory II showed significant improvement 1 year after surgery (p = 0.049). There were no significant changes in Nonverbal Memory I and II, Attention, or Delayed Recall at either the 1-month or 1-year follow-up. CONCLUSIONS Results of the present study indicated that left-sided TSA for hippocampal sclerosis tends to improve verbal memory function with the preservation of other types of memory function. Moreover, right-sided TSA for hippocampal sclerosis can lead to significant improvement in memory function, with memory improvement observed 1 month after right-sided TSA and persisting 1 year after surgery.

Bilateral subfrontal approach for tuberculum sellae meningiomas in long-term postoperative visual outcome

OBJECT Various surgical approaches, such as uni- and bifrontal, frontolateral, and pterional approaches, have been advocated for tuberculum sellae meningiomas. The authors retrospectively reviewed the effectiveness of a bilateral subfrontal approach for tuberculum sellae meningiomas with special attention to ophthalmological outcomes and complications. METHODS Between 1993 and 2009, 34 patients underwent surgery for removal of tuberculum sellae meningiomas at Osaka City University. Tumor size ranged from 14 to 45 mm. Thirty-two of 34 patients presented with visual disturbances before the surgery. The visual functions in all patients were assessed using a visual impairment score (VIS) before and after surgery. Postoperative visual examination was performed 2 weeks after surgery. Long-term follow-up examinations were conducted 1 year after surgery. RESULTS Radical resection (Simpson Grades I and II) was accomplished in 27 patients, and subtotal or partial resection (Simpson Grades III and IV) was achieved in 7. There was no deterioration in postoperative visual outcome. Twenty-nine (90.6%) of 32 patients showed improved VIS compared with preoperative VIS. The average VIS was 38.1 preoperatively, 23.5 in the short-term postoperative period, and 21.8 in the long-term postoperative period. In the short-term postoperative period, the visual function in 6 patients normalized, and visual problems persisted in the remaining 26. Six (23%) of 26 patients showed further improvement in VIS during the long-term follow-up period, and no patient exhibited a worsened VIS during this time. One patient complained of hyposmia after surgery, but there was no indication of related complications such as CSF leakage or frontal brain contusion. CONCLUSIONS The bilateral subfrontal approach was previously avoided because of the relatively high rate of complications in earlier surgical series of tuberculum sellae meningiomas. However, after developments in microsurgical techniques in recent years, the bilateral subfrontal approach can now provide satisfactory visual outcomes with minimal postoperative complications. Careful preservation of the blood supply to optic apparatus and early unroofing of the optic canal using a bilateral subfrontal approach led to further improvement in long-term postoperative visual outcome.

Trans-cerebellomedullary fissure approach with special reference to lateral route.

The trans-cerebellomedullary fissure (CMF) approach provides good exposure of the fourth ventricle without splitting the inferior vermis. The popularly utilized trans-CMF approach is performed in the midline suboccipital approach. However, the trans-CMF approach actually has two routes: medial and lateral. The lateral route is the trans-CMF approach through a lateral foramen magnum approach such as the transcondylar approach, opening the CMF from the lower unilateral side. We studied the surgical anatomy of the CMF and fourth ventricle. Based on the anatomic findings, we adopted the lateral route of the trans-CMF approach for four patients, each with a tumor near the jugular tubercle extending into the fourth ventricle through the CMF. Our study demonstrated that the lateral route of the trans-CMF approach enables sufficient exposure of not only unilateral cerebellopontine cistern but also of the lateral part of the fourth ventricle. A tumor is safely removed by this approach with easy feeder or tumor bed controls, especially if it is anchored at the lateral part of the CMF as is the jugular tubercle meningioma.