Article

Imaging regional variation of cellular proliferation in gliomas using 3'-deoxy-3'-[18F]fluorothymidine positron-emission tomography: an image-guided biopsy study.

Academic Neurosurgery Unit, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Clinical Radiology (Impact Factor: 1.66). 01/2009; 64(1):52-63. DOI: 10.1016/j.crad.2008.01.016
Source: PubMed

ABSTRACT To compare regional variations in uptake of 3'-deoxy-3'- [(18)F]-fluorothymidine (FLT) images using positron-emission tomography (PET) with measures of cellular proliferation from biopsy specimens obtained by image-guided brain biopsies.
Fourteen patients with a supratentorial glioma that required an image-guided brain biopsy were imaged preoperatively with dynamic PET after the administration of FLT. Maps of FLT irreversible uptake rate (K(i)) and standardized uptake value (SUV) were calculated. These maps were co-registered to a gadolinium-enhanced T1-weighted spoiled gradient echo (SPGR) sequence that was used for biopsy guidance, and the mean and maximum K(i) and SUV determined for each biopsy site. These values were correlated with the MIB-1 labelling index (a tissue marker of proliferation) from these biopsy sites.
A total of 57 biopsy sites were studied. Although all measures correlated with MIB-1 labelling index, K(i)(max) provided the best correlation (Pearson coefficient, r=0.68; p<0.001). In low-grade gliomas the K(i)(mean) (+/-SD) was significantly higher than in normal tissue (3.3+/-1.7x10(-3)ml(plasma)/min/ml(tissue) versus 1.2+/-0.7x10(-3)ml(plasma)/min/ml(tissue); p=0.001). High-grade gliomas showed heterogeneous uptake with a mean K(i) of 7.7+/-4x10(-3)ml(plasma)/min/ml(tissue). A threshold K(i)(mean) of 1.8x10(-3) differentiates between normal tissue and tumour (sensitivity 84%, specificity 88%); however, the latter threshold underestimated the extent of tumour in half the cases. SUV closely agreed with K(i) measurements.
FLT PET is a useful marker of cellular proliferation that correlates with regional variation in cellular proliferation; however, it is unable to identify the margin of gliomas.

0 Bookmarks
 · 
73 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Conflicting results on differentiating edema and glioma by diffusion tensor imaging (DTI) are possibly attributable to dissimilar spatial distribution of the lesions. Combining DTI-parameters and enhanced registration might improve prediction. Regions of edema surrounding 22 metastases were compared to tumor-infiltrated regions from WHO grade 2 (12), 3 (10) and 4 (18) gliomas. DTI data was co-registered using Tract Based Spatial Statistics (TBSS), to measure Fractional Anisotropy (FA) and Mean Diffusivity (MD) for white matter only, and relative changes compared to matching reference regions (dFA and dMD). A two-factor principal component analysis (PCA) on metastasis and grade 2 glioma was performed to explore a possible differentiating combined factor. Edema demonstrated equal MD and higher FA compared to grade 2 and 3 glioma (P < 0.001), but did not differ from glioblastoma. Differences were non-significant when corrected for spatial distribution, since reference regions differed strongly (P < 0.001). The second component of the PCA (PCA-C2) did differentiate edema and low-grade tumor (sensitivity 91.7 %, specificity 86.4 %). PCA-C2 scores were plotted voxel-wise as a probability-map, discerning distinct areas of presumed edema or tumor infiltration. Correction of spatial dependency appears essential when differentiating glioma from edema. A tumor-infiltration probability-map is presented, based on supplementary information of multiple DTI parameters and spatial normalization.
    Journal of Neuro-Oncology 07/2014; · 3.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The current standards in radiotherapy of high-grade gliomas (HGG) are based on anatomic imaging techniques, usually computed tomography (CT) scanning and magnetic resonance imaging (MRI). The guidelines vary depending on whether the HGG is a histological grade 3 anaplastic glioma (AG) or a grade 4 glioblastoma multiforme (GBM). For AG, T2-weighted MRI sequences plus the region of contrast enhancement in T1 are considered for the delineation of the gross tumor volume (GTV), and an isotropic expansion of 15 to 20 mm is recommended for the clinical target volume (CTV). For GBM, the Radiation Therapy Oncology Group favors a two-step technique, with an initial phase (CTV1) including any T2 hyperintensity area (edema) plus a 20 mm margin treated with up to 46 Gy in 23 fractions, followed by a reduction in CTV2 to the contrast enhancement region in T1 with an additional 25 mm margin. The European Organisation of Research and Treatment of Cancer recommends a single-phase technique with a unique GTV, which comprises the T1 contrast enhancement region plus a margin of 20 to 30 mm. A total dose of 60 Gy in 30 fractions is usually delivered for GBM, and a dose of 59.4 Gy in 33 fractions is typically given for AG. As more than 85% of HGGs recur in field, dose-escalation studies have shown that 70 to 75 Gy can be delivered in 6 weeks with relevant toxicities developing in <10% of the patients. However, the only randomized dose-escalation trial, in which the boost dose was guided by conventional MRI, did not show any survival advantage of this treatment over the reference arm. HGGs are amongst the most infiltrative and heterogeneous tumors, and it was hypothesized that the most highly aggressive areas were missed; thus, better visualization of these high-risk regions for radiation boost could decrease the recurrence rate. Innovations in imaging and linear accelerators (LINAC) could help deliver the right doses of radiation to the right subvolumes according to the dose-painting concept. Advanced imaging techniques provide functional information on cellular density (diffusion MRI), angiogenesis (perfusion MRI), metabolic activity and cellular proliferation [positron emission tomography (PET) and magnetic resonance spectroscopy (MRS)]. All of these non-invasive techniques demonstrated good association between the images and histology, with up to 40% of HGGs functionally presenting a high activity within the non-contrast-enhanced areas in T1. New LINAC technologies, such as intensity-modulated and stereotactic radiotherapy, help to deliver a simultaneous integrated boost (SIB) > 60 Gy. Trials delivering a SIB into a biological GTV showed the feasibility of this treatment, but the final results, in terms of clinical benefits for HGG patients, are still pending. Many issues have been identified: the variety of MRI and PET machines (and amino-acid tracers), the heterogeneity of the protocols used for image acquisition and post-treatment, the geometric distortion and the unreliable algorithms for co-registration of brain anatomy with functional maps, and the semi-quiescent but highly invasive HGG cells. These issues could be solved by the homogenization of the protocols and software applications, the simultaneous acquisition of anatomic and functional images (PET-MRI machines), the combination of complementary imaging tools (perfusion and diffusion MRI), and the concomitant addition of some ad hoc targeted drugs against angiogenesis and invasiveness to chemoradiotherapy. The integration of these hybrid data will construct new synthetic metrics for fully individualized treatments.
    Ai zheng = Aizheng = Chinese journal of cancer 01/2014; 33(1):16-24.
  • [Show abstract] [Hide abstract]
    ABSTRACT: 3'-deoxy-3'-18F-fluorothymidine ([(18)F] FLT) PET has been proven to be of value in diagnosis and assessment of glioma grading, in differentiating tumor recurrence from necrosis, in response assessment and in predicting overall survival (OS) in the primary high grade glioma. In this study, we evaluated the value of [(18)F] FLT PET-CT in predicting the OS of patients with recurrent malignant glioma.
    Nuclear medicine and biology. 05/2014;