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Background/purpose The prognostic value of defining subcategories of gliomas is still controversial. This study aims to determine the utility of relative cerebral blood volume (rCBV) in predicting clinical response in patients with low-grade glioma at multiple institutions. Materials and methods Sixty-nine patients were studied with dynamic susceptibility contrast-enhanced perfusion MRI at two institutions. The pathologic diagnoses of the low-grade gliomas were 34 astrocytomas, 20 oligodendroglioma, 9 oligoastrocytomas, 1 ganglioglioma and 5 with indeterminate histology. Wilcoxon tests were used to compare patients in different response categories with respect to baseline rCBV. Kaplan–Meier curve and log-rank tests were used to predict the association of rCBV with time to progression. Results At both institutions, patients with an adverse event (progressive disease or death) had a significantly higher baseline rCBV than those without (complete response or stable disease) (p value = 0.0138). The odds ratio for detecting an adverse event when using rCBV was 1.87 (95% confidence interval: 1.14–3.08). rCBV was significantly negatively associated with time to progression (p = 0.005). The median time to progression among subjects with rCBV > 1.75 was 365 days, while there was 95% confidence that the median time to progression was at least 889 days among subjects with rCBV Conclusion Our study suggests not only that rCBV measurements correlate well with time to progression or death, but also that the findings can be replicated across institutions, which supports the application of rCBV as an adjunct to pathology in predicting glioma biology.

Quantitative magnetisation transfer imaging (qMTI) is an extension of conventional MT techniques and allows the measurement of parameters that reflect tissue ultrastructure through the properties of macromolecule-bound protons; these include the bound proton fraction and the relaxation times of free and bound proton pools. It has been used in multiple sclerosis and Alzheimer's disease, and has shown changes in some of the parameters, particularly the bound proton fraction. The purpose of this pilot study was to assess whether qMTI could distinguish between gliomas and normal brain tissue, and provide proof of principle for its use in tumour characterisation. Eight subjects [three men, five women; mean age, 44 years; range, 27-66 years; seven World Health Organization (WHO) Grade II, one Grade III] with biopsy-proven glioma were imaged with a structural MRI protocol that included three-dimensional qMTI. qMTI parameters were extracted from regions of interest selected from different tumour components visible on conventional MR sequences, normal-appearing peritumoral tissue and distant normal-appearing white matter. All patients gave informed consent and the study was approved by the Local Research Ethics Committee. Almost all of the qMTI parameters detected abnormalities in both glioma and the peritumoral region relative to the distant white matter. In particular, the bound proton fraction was reduced significantly from 6.0 percentage units (pu) [standard deviation (SD), 0.5 pu] in normal-appearing white matter to 1.7 pu (SD = 0.5 pu) in solid tumour and 2.2 pu (SD = 0.5 pu) in peritumoral areas. This work shows that qMTI reveals abnormalities, not only in glioma, but also in the apparently normal tissue surrounding the conventionally defined tumour. Thus, qMTI shows promise for tumour characterisation and for studying tumour boundaries. These preliminary data justify larger studies in a range of different tumour types and grades.

To prospectively compare tumor volume, relative cerebral blood volume (rCBV), and apparent diffusion coefficient (ADC) and short-term changes of these parameters as predictors of time to malignant transformation and time to death in patients with low-grade gliomas (LGGs).Patients gave written informed consent for this institutional ethics committee-approved study. Patients with histologically proved LGGs underwent conventional, perfusion-weighted, and diffusion-weighted magnetic resonance (MR) imaging at study entry and at 6 months. At both time points, tumor volume, maximum rCBV, and ADC histogram measures were calculated. Patient follow-up consisted of MR imaging every 6 months and clinical examinations. To investigate the association between MR imaging variables and time to progression and time to death, a Cox regression curve was applied at study entry and at 6 months. The models were corrected for age, sex, and histologic findings.Thirty-four patients (22 men, 12 women; mean age, 42 years) with histologically proved LGGs (eight oligodendrogliomas, 20 astrocytomas, and six oligoastrocytomas) were followed up clinically and radiologically for a median of 2.6 years (range, 0.4-5.5 years). Tumor growth over the course of 6 months was the best predictor of time to transformation, independent of rCBV, diffusion histogram parameters, age, sex, and histologic findings. When only single-time-point measurements were compared, tumor volume helped predict outcome best and was the only independent predictor of time to death (P.02).Six-month tumor growth helps predict outcome in patients with LGG better than parameters derived from perfusion- or diffusion-weighed MR imaging. Tumor growth can readily be calculated from volume measurements on images acquired with standard MR imaging protocols and may well prove most useful among various MR imaging findings in clinical practice.

To prospectively perform longitudinal magnetic resonance (MR) perfusion imaging of conservatively treated low-grade gliomas to determine whether relative cerebral blood volume (rCBV) changes precede malignant transformation as defined by conventional MR imaging and clinical criteria.All patients gave written informed consent for this institutional ethics committee-approved study. Thirteen patients (seven men, six women; age range, 29-69 years) with biopsy-proved low-grade glioma treated only with antiepileptic drugs were examined longitudinally with susceptibility-weighted perfusion, T2-weighted, fluid-attenuated inversion recovery, and high-dose contrast material-enhanced T1-weighted MR imaging at 6-month intervals to date or until malignant transformation was diagnosed. Student t tests were used to determine differences in rCBV values between "transformers" and "nontransformers" at defined time points throughout study follow-up.Seven patients showed progression to high-grade tumors between 6 and 36 months (mean, 22.3 months), and disease in six patients remained stable over a period of 12-36 months (mean, 23 months). Transformers had a slightly (but not statistically significantly) higher group mean rCBV than nontransformers at the point of study entry (1.93 vs 1.31). In nontransformers, the rCBV remained relatively stable and increased to only 1.52 over a mean follow-up of 23 months. In contrast, transformers showed a continuous increase in rCBV up to the point of transformation, when contrast enhancement became apparent on T1-weighted images. The group mean rCBV was 5.36 at transformation but also showed a significant increase from the initial study at 12 months (3.14, P = .022) and at 6 months (3.65, P = .049) before transformation. Rates of rCBV change between two successive time points were also significantly higher in transformers than in nontransformers.In transforming low-grade glioma, susceptibility-weighted MR perfusion imaging can demonstrate significant increases in rCBV up to 12 months before contrast enhancement is apparent on T1-weighted MR images.

PURPOSE: To quantify subtle gadolinium (Gd) enhancement (signal increase) in whole-tumor histograms and optimize their ability to predict subsequent malignant transformation in low-grade gliomas (LGGs). MATERIALS AND METHODS: We analyzed histograms from 21 adult subjects with LGGs (eight nontransformers and 13 transformers) who had been imaged every six months for periods of two to five years. Before transformation these tumors were reported as radiologically non-enhancing. Imaging included a T(1)-weighted volume sequence before and after a double dose of Gd-DTPA contrast agent. Image data sets were spatially registered and subtracted to obtain maps of percent enhancement (%E). Tumor outlines were defined on fluid-attenuated inversion recovery (FLAIR) images, and the volumes were calculated. Histogram tails were analyzed to obtain the volume (mL) of subtly enhancing tissue (%E > 10%). RESULTS: Baseline enhancing volumes were higher for Ts than for NTs (P < 0.005). Kaplan-Meier survival curves for a threshold of 4 mL showed clear differences at five years (P < 0.04). Pretransformation examinations predicted transformation (corrected threshold = 3.0 mL, P = 0.011). CONCLUSION: Clear histogram differences at presentation suggest that the process of transformation starts very early. It is now possible to identify individuals at high risk for transformation at baseline by quantifying the volume of subtly enhancing tumor tissue, and such findings could have an impact on patient management.

The subtypes of glioma are known to have different prognosis and response to treatment. The purpose of this work was to investigate whether apparent diffusion coefficient (ADC) histograms of untreated low-grade astrocytomas and oligodendrogliomas exhibit different characteristics due to their biological differences, and whether a diagnosis of tumour subtype can be made at presentation using the histogram alone, which, if possible, would have an impact on clinical practise. Fifteen patients with astrocytoma (AC) [11 male (mean age +/- standard deviation) 40 +/- 11 years], nine with oligodendroglioma (OD) (four male, 45 +/- 13 years) and three with oligoastrocytoma (OA) (two male, 60 +/- 11 years) were recruited and diffusion-weighted images (b = 0 and 1000 s mm(-2)) were acquired every 6 months to date or until malignant transformation. Whole tumour ADC histograms were calculated, a multiple discriminant analysis was performed and quantitative morphological parameters extracted, the AC and OD subtypes were then compared using Student's unpaired t-test. Classification of the histograms was also performed. ODs had significantly lower group ADC values than ACs and up to 83% of the subjects could be correctly classified into the OD and AC groups by reference to the histogram. The group differences were most significant for the multiple discriminant analysis (p = 1 x 10(-5)) and at the 10th centile point [AC = 1170 +/- 170, OD = (1030 +/- 80) x 10(-6) mm(2) s(-1)] (p = 0.01). ODs have a lower ADC than ACs with differences throughout the histogram. Both tumour types show similar intra-tumour heterogeneity, as seen from the equal group peak heights, but ACs shows more intra-group heterogeneity. ADC histogram analysis may aid non-invasive sub-classification of low-grade glioma histological subtypes.

SUMMARY: We assessed the influence of inclusion (method 1) and exclusion (method 2) of intratumoral vessels when determining maximum relative cerebral blood volume (rCBVmax) in 3 types of low-grade gliomas (LGGs): astrocytomas, oligoastrocytomas, and oligodendrogliomas. Method 1 yielded significantly higher mean rCBVmax than method 2. However, only method 2 demonstrated a significant (P = .026) association between rCBVmax and membership of a differently ranked histologic category. Exclusion of intratumoral vessels appears, therefore, preferable when determining rCBVmax in LGGs.

Background Adult low-grade gliomas (LGG) are usually WHO grade II and have a propensity to transform into malignant gliomas at some point in their natural history. Prognostic factors for patients treated with radiotherapy include increasing age and tumour diameter, but may not be applicable to patients who have not received any oncological treatment. We have carried out a prospective multimodality imaging study of 47 untreated adult patients with supratentorial LGG to determine which factors are independently associated with a poor prognosis, using time to progression as the primary endpoint. Methods Patients were recruited from the neuro-oncology clinic and followed up from January 1999 to December 2006. Baseline clinical and radiological data were collected and Kaplan–Meier, univariate and multivariate analysis using Cox proportional hazards regression model, were carried out. Results 28 patients (60%) had progressed by the end of the study. Median progression-free survival was 35.4 (9.9–93.3) months. In univariate analysis, 6 out of 12 prognostic variables reached significance at the 10% level. Multivariate analysis showed that only baseline tumour volume as well as lead time between first seizure and first MRI study were significant at the 5% level. Conclusions Tumour volume, measured with an easily reproducible method on standard MR sequences, is of prognostic value in predicting tumour progression in patients with untreated LGG.