Natasha L. Robinette

Accurate Differentiation of Recurrent Gliomas from Radiation Injury by Kinetic Analysis of α-11C-Methyl-l-Tryptophan PET

PET of amino acid transport and metabolism may be more accurate than conventional neuroimaging in differentiating recurrent gliomas from radiation-induced tissue changes. α-11C-methyl-l-tryptophan (11C-AMT) is an amino acid PET tracer that is not incorporated into proteins but accumulates in gliomas, mainly because of tumoral transport and metabolism via the immunomodulatory kynurenine pathway. The aim of this study was to evaluate the usefulness of 11C-AMT PET supplemented by tracer kinetic analysis for distinguishing recurrent gliomas from radiation injury. Methods: Twenty-two 11C-AMT PET scans were obtained in adult patients who presented with a lesion suggestive of tumor recurrence on conventional MRI 1–6 y (mean, 3 y) after resection and postsurgical radiation of a World Health Organization grade II–IV glioma. Lesional standardized uptake values were calculated, as well as lesion-to-contralateral cortex ratios and 2 kinetic 11C-AMT PET parameters (volume of distribution [VD], characterizing tracer transport, and unidirectional uptake rate [K]). Tumor was differentiated from radiation-injured tissue by histopathology (n = 13) or 1-y clinical and MRI follow-up (n = 9). Accuracy of tumor detection by PET variables was assessed by receiver-operating-characteristic analysis. Results: All 11C-AMT PET parameters were higher in tumors (n = 12) than in radiation injury (n = 10) (P ≤ 0.012 in all comparisons). The lesion-to-cortex K-ratio most accurately identified tumor recurrence, with highly significant differences both in the whole group (P < 0.0001) and in lesions with histologic verification (P = 0.006); the area under the receiver-operating-characteristic curve was 0.99. A lesion-to-cortex K-ratio threshold of 1.39 (i.e., a 39% increase) correctly differentiated tumors from radiation injury in all but 1 case (100% sensitivity and 91% specificity). In tumors that were high-grade initially (n = 15), a higher lesion-to-cortex K-ratio threshold completely separated recurrent tumors (all K-ratios ≥ 1.70) from radiation injury (all K-ratios < 1.50) (100% sensitivity and specificity). Conclusion: Kinetic analysis of dynamic 11C-AMT PET images may accurately differentiate between recurrent World Health Organization grade II–IV infiltrating gliomas and radiation injury. Separation of unidirectional uptake rates from transport can enhance the differentiating accuracy of 11C-AMT PET. Applying the same approach to other amino acid PET tracers might also improve their ability to differentiate recurrent gliomas from radiation injury.

Differentiation of Glioblastomas from Metastatic Brain Tumors by Tryptophan Uptake and Kinetic Analysis: A Positron Emission Tomographic Study with Magnetic Resonance Imaging Comparison

Differentiating high-grade gliomas from solitary brain metastases is often difficult by conventional magnetic resonance imaging (MRI); molecular imaging may facilitate such discrimination. We tested the accuracy of α[11C]methyl-L-tryptophan (AMT)–positron emission tomography (PET) to differentiate newly diagnosed glioblastomas from brain metastases. AMT-PET was performed in 36 adults with suspected brain malignancy. Tumoral AMT accumulation was measured by standardized uptake values (SUVs). Tracer kinetic analysis was also performed to separate tumoral net tryptophan transport (by AMT volume of distribution [VD]) from unidirectional uptake rates using dynamic PET and blood input function. Differentiating the accuracy of these PET variables was evaluated and compared to conventional MRI. For glioblastoma/metastasis differentiation, tumoral AMT SUV showed the highest accuracy (74%) and the tumor/cortex VD ratio had the highest positive predictive value (82%). The combined accuracy of MRI (size of contrast-enhancing lesion) and AMT-PET reached up to 93%. For ring-enhancing lesions, tumor/cortex SUV ratios were higher in glioblastomas than in metastatic tumors and could differentiate these two tumor types with > 90% accuracy. These results demonstrate that evaluation of tryptophan accumulation by PET can enhance pretreatment differentiation of glioblastomas and metastatic brain tumors. This approach may be particularly useful in patients with a newly diagnosed solitary ring-enhancing mass.

Increased tryptophan uptake on PET has strong independent prognostic value in patients with a previously treated high-grade glioma

BACKGROUND Previously, we demonstrated the high accuracy of alpha-[(11)C]methyl-L-tryptophan (AMT) PET for differentiating recurrent gliomas from radiation injury. The present study evaluated the prognostic value of increased AMT uptake in patients with previously treated high-grade glioma. METHODS AMT-PET was performed in 39 patients with suspected recurrence of World Health Organization grades III-IV glioma following surgical resection, radiation, and chemotherapy. Mean and maximum standardized uptake values (SUVs) and unidirectional AMT uptake (K) were measured in brain regions suspicious for tumor and compared with the contralateral cortex (ie, background). Optimal cutoff thresholds for 1-year survival prediction were determined for each AMT parameter and used for calculating the prognostic value of high (above threshold) versus low (below threshold) values for post-PET overall survival (OS). RESULTS In univariate analyses, 1-year survival was strongly associated with 3 AMT parameters (SUVmax, SUVmean, and tumor-to-background K-ratio; odds ratios: 21.3-25.6; P ≤ .001) and with recent change in MRI contrast enhancement (odds ratio: 14.7; P = .02). Median OS was 876 days in the low- versus 177 days in the high-AMT groups (log-rank P < .001). In multivariate analyses, all 3 AMT parameters remained strong predictors of survival: high AMT values were associated with unfavorable 1-year survival (binary regression P ≤ .003) and shorter overall survival in the whole group (Cox regression hazard ratios: 5.3-10.0) and in patients with recent enhancement change on MRI as well (hazard ratios: 7.0-9.3; P ≤ .001). CONCLUSION Increased AMT uptake on PET is highly prognostic for 1-year and overall survival, independent of MRI contrast enhancement and other prognostic factors in patients with a previously treated high-grade glioma.

Trauma patterns, symptoms, and complications associated with external auditory canal fractures

External auditory canal (EAC) trauma, although rare, can have significant long‐term adverse outcomes. This study aims to investigate the frequency, treatment, and complications of external ear canal injury in association with mandibular and temporal bone trauma.

Unresectable Extraskeletal Myxoid Chondrosarcoma of the Neck: Early Tumor Response to Chemoradiotherapy

Extraskeletal myxoid chondrosarcoma (EMC) rarely occurs in the head and neck and is generally managed with primary surgery. To our knowledge, no cases of unresectable EMC of the neck have been reported. We present a case of an unresectable EMC treated with chemotherapy and radiation, and highlight the exceptional early response to therapy.

Multi-modal imaging of tumor cellularity and Tryptophan metabolism in human Gliomas

BackgroundTo assess gliomas using image-based estimation of cellularity, we utilized isotropic diffusion spectrum imaging (IDSI) on clinically feasible diffusion tensor imaging (DTI) and compared it with amino acid uptake measured by α[11C]methyl-L-tryptophan positron emission tomography (AMT-PET).MethodsIn 10 patients with a newly-diagnosed glioma, metabolically active tumor regions were defined in both FLAIR hyperintense areas and based on increased uptake on AMT-PET. A recently developed independent component analysis with a ball and stick model was extended to perform IDSI in clinical DTI data. In tumor regions, IDSI was used to define tumor cellularity which was compared between low and high grade glioma and correlated with the glioma proliferative index.ResultsThe IDSI-derived cellularity values were elevated in both FLAIR and AMT-PET-derived regions of high-grade gliomas. ROC curve analysis found that the IDSI-derived cellularity can provide good differentiation of low-grade from high-grade gliomas (accuracy/sensitivity/specificity of 0.80/0.80/0.80). . Both apparent diffusion coefficient (ADC) and IDSI-derived cellularity showed a significant correlation with the glioma proliferative index (based on Ki-67 labeling; R = 0.95, p < 0.001), which was particularly strong when the tumor regions were confined to areas with high tryptophan uptake excluding areas with peritumoral edema.ConclusionIDSI-MRI combined with AMT-PET may provide a multi-modal imaging tool to enhance pretreatment assessment of human gliomas by evaluating tumor cellularity and differentiate low-grade form high-grade gliomas.

Clinical Significance of Tryptophan Metabolism in the Nontumoral Hemisphere in Patients with Malignant Glioma

α-11C-methyl-l-tryptophan (AMT) PET allows evaluation of brain serotonin synthesis and can also track upregulation of the immunosuppressive kynurenine pathway in tumor tissue. Increased AMT uptake is a hallmark of World Health Organization grade III–IV gliomas. Our recent study also suggested decreased frontal cortical AMT uptake in glioma patients contralateral to the tumor. The clinical significance of extratumoral tryptophan metabolism has not been established. In the present study, we investigated clinical correlates of tryptophan metabolic abnormalities in the nontumoral hemisphere of glioma patients. Methods: Standardized AMT uptake values (SUVs) and the uptake rate constant of AMT (K [mL/g/min], a measure proportional to serotonin synthesis in nontumoral gray matter) were quantified in the frontal and temporal cortex and thalamus in the nontumoral hemisphere in 77 AMT PET scans of 66 patients (41 men, 25 women; mean age ± SD, 55 ± 15 y) with grade III–IV gliomas. These AMT values were determined before treatment in 35 and after treatment in 42 patients and were correlated with clinical variables and survival. Results: AMT uptake in the thalamus showed a moderate age-related increase before treatment (SUV, r = 0.39, P = 0.02) but decrease after treatment (K, r = −0.33, P = 0.057). Women had higher thalamic SUVs before treatment (P = 0.037) and higher thalamic (P = 0.013) and frontal cortical K values (P = 0.023) after treatment. In the posttreatment glioma group, high thalamic SUVs and high thalamocortical SUV ratios were associated with short survival in Cox regression analysis. The thalamocortical ratio remained strongly prognostic (P < 0.01) when clinical predictors, including age, glioma grade, and time since radiotherapy, were entered in the regression model. Long interval between radiotherapy and posttreatment AMT PET as well as high radiation dose affecting the thalamus were associated with lower contralateral thalamic or cortical AMT uptake values. Conclusion: These observations provide evidence for altered tryptophan uptake in contralateral cortical and thalamic brain regions in glioma patients after initial therapy, suggesting treatment effects on the serotonergic system. Low thalamic tryptophan uptake appears to be a strong, independent predictor of long survival in patients with previous glioma treatment.

Pretreatment computed tomographic gross tumor volume as predictor of persistence of tracheostomy and percutaneous endoscopic gastrostomy tube in patients undergoing larynx preservation

Although larynx preservation affords patients improvements in laryngectomy‐free survival, little has been reported regarding the functional outcomes after larynx preservation. The purpose of this study was to report the predictive value of pretreatment CT‐gross tumor volume (GTV) for persistence of tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube in larynx preservation patients.

Low tryptophan uptake in contrast-enhancing lesions predicts long-term survival in patients with a previously treated glioblastoma: A pet study

WCN 2013 No: 868 Topic: 36 — Other topic Low tryptophan uptake in contrast-enhancing lesions predicts long-term survival in patients with a previously treated glioblastoma: A pet study C. Juhasz, D.O. Kamson, N.L. Robinette, O. Muzik, P.K. Chakraborty, G.R. Barger, S. Mittal. Neurology and Pediatrics, Wayne State University, USA; PET Center and Translational Imaging Laboratory, Childrens Hospital ofMichigan, USA; Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA; Radiology, Wayne State University, Detroit, MI, USA; Neurology,Wayne State University, Detroit, MI, USA; Neurosurgery, Wayne State University, Detroit, MI, USA Background: MRI has limited prognostic value in patients with a previously treated glioblastoma. Positron emission tomography (PET) imaging with alpha[C]methyl-L-tryptophan (AMT), a radiotracer tracking tryptophan transport and metabolism via the immunosuppressive kynurenine pathway, can effectively differentiate glioma recurrence from radiation injury. Objective: To evaluate the prognostic value of AMT uptake measured on post-treatment PET in patients with glioblastoma treated with surgery followed by chemoradiation. Patients and methods: AMT-PET was performed in 32 patients (mean age: 60 years) with a previously treated glioblastoma. The PET scans were done 6–62 months after initial surgery after MRI demonstrated a contrast-enhancing lesion suspicious for tumor progression. AMT uptake values were measured (on summed activity images 30–55 min after tracer injection) in contrast-enhancing regions and contralateral cortex, and correlated with survival after PET. A receiver operating characteristic analysis was performed to determine the optimal cutoff threshold to predict 1-year survival. Results: At the end of follow-up, 23 patients were deceased and 9 alive (for up to 83 months). A cutoff threshold of 1.65 for lesion/cortex AMT uptake ratios provided 82% sensitivity/specificity for 1-year survival after PET. Age-corrected Cox regression analysis showed a strong association between above-threshold AMT uptake ratios and shorter survival (odds-ratio: 4.3 [1.5–12.5], p = 0.005). Below-threshold AMT uptake ratios (n = 13) were associated with an additional year median survival compared to patients with high ratios (618 days vs. 257 days). Conclusion: Low AMT uptake on PET, measured in contrast-enhancing lesions suspicious for tumor progression, predicts long-term survival in patients with a previously treated glioblastoma. doi:10.1016/j.jns.2013.07.2139 Abstract — WCN 2013 No: 1131 Topic: 36 — Other topic Sleep curtailment is associated with altered autonomic tonus in normal-weight individuals W. Moraes, D. Poyares, L. Bittencourt, S. Tufik. Sleep Medicine, Universidade de Sao Paulo, Brazil; Psychobiology, UNIFESP,

Multimodal Imaging-defined Subregions in Newly-diagnosed Glioblastoma: Impact on Overall Survival

BACKGROUND Although glioblastomas are heterogeneous brain-infiltrating tumors, their treatment is mostly focused on the contrast-enhancing tumor mass. In this study, we combined conventional MRI, diffusion-weighted imaging (DWI), and amino acid PET to explore imaging-defined glioblastoma subregions and evaluate their potential prognostic value. METHODS Contrast-enhanced T1, T2/fluid attenuated inversion recovery (FLAIR) MR images, apparent diffusion coefficient (ADC) maps from DWI, and alpha-[11C]-methyl-L-tryptophan (AMT)-PET images were analyzed in 30 patients with newly diagnosed glioblastoma. Five tumor subregions were identified based on a combination of MRI contrast enhancement, T2/FLAIR signal abnormalities, and AMT uptake on PET. ADC and AMT uptake tumor/contralateral normal cortex (T/N) ratios in these tumor subregions were correlated, and their prognostic value was determined. RESULTS A total of 115 MRI/PET-defined subregions were analyzed. Most tumors showed not only a high-AMT uptake (T/N ratio > 1.65, N = 27) but also a low-uptake subregion (N = 21) within the contrast-enhancing tumor mass. High AMT uptake extending beyond contrast enhancement was also common (N = 25) and was associated with low ADC (r = -0.40, P = 0.05). Higher AMT uptake in the contrast-enhancing tumor subregions was strongly prognostic for overall survival (hazard ratio: 7.83; 95% CI: 1.98-31.02, P = 0.003), independent of clinical and molecular genetic prognostic variables. Nonresected high-AMT uptake subregions predicted the sites of tumor progression on posttreatment PET performed in 10 patients. CONCLUSIONS Glioblastomas show heterogeneous amino acid uptake with high-uptake regions often extending into non-enhancing brain with high cellularity; nonresection of these predict the site of posttreatment progression. High tryptophan uptake values in MRI contrast-enhancing tumor subregions are a strong, independent imaging marker for longer overall survival.