<Superscript>11</Superscript>C-methionine (MET) and <Superscript>18</Superscript>F-fluorothymidine (FLT) PET in patients with newly diagnosed glioma

Purpose  The purpose of this prospective study was to clarify the individual and combined role of l-methyl-¹¹C-methionine-positron emission tomography (MET-PET) and 3′-deoxy-3′-[¹⁸F]fluorothymidine (FLT)-PET in tumor detection, noninvasive grading, and assessment of the cellular proliferation rate in newly diagnosed histologically verified gliomas of different grades. Materials and methods  Forty-one patients with newly diagnosed gliomas were investigated with MET-PET before surgery. Eighteen patients were also examined with FLT-PET. MET and FLT uptakes were assessed by standardized uptake value of the tumor showing the maximum uptake (SUV_max), and the ratio to uptake in the normal brain parenchyma (T/N ratio). All tumors were graded by the WHO grading system using surgical specimens, and the proliferation activity of the tumors were determined by measuring the Ki-67 index obtained by immunohistochemical staining. Results  On semiquantitative analysis, MET exhibited a slightly higher sensitivity (87.8%) in tumor detection than FLT (83.3%), and both tracers were 100% sensitive for malignant gliomas. Low-grade gliomas that were false negative on MET-PET also were false negative on FLT-PET. Although the difference of MET SUV_max and T/N ratio between grades II and IV gliomas was statistically significant (P < 0.001), there was a significant overlap of MET uptake in the tumors. The difference of MET SUV_max and T/N ratio between grades II and III gliomas was not statistically significant. Low-grade gliomas with oligodendroglial components had relatively high MET uptake. The difference of FLT SUV_max and T/N ratio between grades III and IV gliomas was statistically significant (P < 0.01). Again, the difference of FLT SUV_max and T/N ratio between grades II and III gliomas was not statistically significant. Grade III gliomas with non-contrast enhancement on MR images had very low FLT uptake. In 18 patients who underwent PET examination with both tracers, a significant but relatively weak correlation was observed between the individual SUV_max of MET and FLT (r = 0.54, P < 0.05) and T/N ratio of MET and FLT (r = 0.56, P < 0.05). Total FLT uptake in the tumor had a higher correlation (r = 0.89, P < 0.001) with Ki-67 proliferation index than MET uptake (r = 0.49, P < 0.01). Conclusions  PET studies using MET and FLT are useful for tumor detection in newly diagnosed gliomas. However, there is no complimentary information in tumor detection with simultaneous measurements of MET- and FLT-PET in low grade gliomas. FLT-PET seems to be superior than MET-PET in noninvasive tumor grading and assessment of proliferation activity in gliomas of different grades.     

FET PET for the evaluation of untreated gliomas: correlation of FET uptake and uptake kinetics with tumour grading

Purpose Treatment and prognosis of gliomas depend on their histological tumour grade. The aim of the study was to evaluate the potential of [¹⁸F]fluoroethyltyrosine (FET) PET for non-invasive tumour grading in untreated patients. Methods Dynamic FET PET studies were performed in 54 patients who, based on MRI, were estimated to have low grade (LG; n = 20), intermediate (WHO II–III; n = 4) or high grade (HG; n = 30) tumours. For standard evaluation, tumour SUV_max and the ratio to background (SUV_max/BG) were calculated (sum image: 20–40 min). For dynamic evaluation, mean SUV values within a 90% isocontour ROI (SUV90) and the SUV90/BG ratios were determined for each time frame to evaluate the course of FET uptake. Results were correlated with histopathological findings from PET-guided stereotactic biopsies. Results Histology revealed gliomas in all patients. Using the standard method a statistically significant difference (p = 0.001) was found between LG (n = 20; SUV_max/BG: 2.16 ± 0.98) and HG (n = 34; SUV_max/BG: 3.29 ± 1.06) gliomas (opt. threshold 2.58: SN71%/SP85%/area under ROC curve [AUC]:0.798), however, with a marked overlap between WHO II to IV tumours. Time activity curves showed slight increase in LG, whereas HG tumours presented with an early peak (10–20 min) followed by a decrease. Dynamic evaluation successfully separated LG from HG gliomas with higher diagnostic accuracy (SN94%/SP100%/AUC:0.967). Conclusions Based on the ratio-based method, a statistically significant difference was found between LG and HG gliomas. Due to the interindividual variability, however, no reliable individual grading was possible. In contrast, dynamic evaluation allowed LG and HG gliomas to be differentiated with high diagnostic power and, thus, should supplement the conventional method.     

Value of <Emphasis Type="Italic">O</Emphasis>-(2-[<Superscript>18</Superscript>F]fluoroethyl)-<Emphasis Type="SmallCaps">l</Emphasis>-tyrosine PET for the diagnosis of recurrent glioma

Purpose The prognosis of patients with recurrent gliomas depends on reliable and early diagnosis of tumour recurrence after initial therapy. In this context, magnetic resonance imaging (MRI) and computed tomography (CT) often fail to differentiate between radiation- and tumour-induced contrast enhancement. Furthermore, absence of contrast enhancement, or even of ¹⁸F-fluorodeoxyglucose uptake in PET, does not exclude recurrence. The aim of this study was to establish the diagnostic value of O-(2-[¹⁸F]fluoroethyl)-l-tyrosine (FET) PET in recurrent gliomas.Methods Fifty-three patients with glioma (primary grading: 27=WHO grade IV, 16=grade III, 9=grade II, 1=grade I) and clinically suspected recurrence underwent FET PET scans 4–180 months after different treatment modalities. For semiquantitative evaluation, maximal SUV (SUV_max) and mean SUV within 80% and 70% isocontour thresholds (SUV₈₀/SUV₇₀) were evaluated and the respective ratios to the background (BG) were calculated. PET results were correlated with MRI/CT, clinical follow-up or biopsy findings.Results All patients presented with FET uptake, of varying intensity, in the area of the primary tumour after initial therapy. In the 42 patients with confirmed recurrence, there was additional distinct focal FET uptake with significantly higher values compared with those in the 11 patients without clinical signs of recurrence and showing only low and homogeneous FET uptake at the margins of the resection cavity. With respect to tumour grading, there was a slight but non-significant increase from WHO II (SUV_max/BG: 2.53±0.28) to WHO III (SUV_max/BG: 2.84±0.49) and WHO IV (SUV_max/BG: 3.55±1.07) recurrence.Conclusion FET PET reliably distinguishes between post-therapeutic benign lesions and tumour recurrence after initial treatment of low- and high-grade gliomas.     

Immunohistochemical analysis on cyclooxygenase-2 for wound age determination

Immunohistochemical study combined with morphometry was carried out to examine the expression of cyclooxygenase-2 (COX-2) using 60 human skin wounds of different ages: group I, 0–4 h (n = 11); II, 8 h–2 days (n = 21); III, 3–9 days (n = 14); and IV, 12–21 days (n = 14). In wound specimens aged 2 h to 2 days, anti-myeloperoxidase-positive neutrophils observed at the wound site expressed immunopositive reaction to COX-2. In wound specimens of more than 3 days, CD68-positive macrophages as well as neutrophils were positively immunostained with anti-COX-2. In group II, all 21 wound samples had COX-2-positive ratios of >40 %, and 15 out of them showed >50 %. In group III, only three wound samples with the postinfliction intervals of 3 days showed positive ratios of 40–50 % and the remaining 11 cases less than 40 %. In groups I and IV, all 25 wound specimens had COX-2-positive ratio of <40 %. With regard to the practical applicability with forensic safety, these observations suggested that a COX-2-positive ratio of >40 % indicated a wound age of 8 h to 3 days. Moreover, COX-2-positive ratios, considerably exceeding a ratio of 50 %, indicate a wound age of 8 h to 2 days. Collectively, COX-2 would be a useful marker for the determination of early wound age.     

3-[123I]Iodo-alpha-methyl-L-tyrosine uptake in cerebral gliomas: relationship to histological grading and prognosis

3-[123I]Iodo-alpha-methyl-L-tyrosine (IMT) is employed clinically as a tracer of amino acid transport in brain tumours using single-photon emission tomography (SPET). This study investigates the role of IMT SPET in the non-invasive histological grading and prognostic evaluation of cerebral gliomas. The files of patients investigated by IMT SPET in our clinic between 1988 and 1996 were evaluated retrospectively. Complete follow-up was available for 58 patients with cerebral gliomas investigated by IMT SPET shortly after tumour diagnosis. Seventeen patients had low-grade gliomas (WHO grade II), 14 had anaplastic gliomas (WHO grade III) and 27 had glioblastomas (WHO grade IV). Thirty-six cases were primary tumours and 22 cases, recurrences. Maximal and mean tumour-to-brain (T/B) ratios of IMT uptake at the first IMT SPET investigation were related to histological grading and survival time. Patients with low-grade gliomas showed significantly longer survival than patients with high-grade (grade III or IV) tumours. Gliomas without contrast enhancement on computed tomography or magnetic resonance imaging scans were associated with longer patient survival than tumours with contrast enhancement. The T/B ratios of IMT SPET showed no differences in relation to histological grading [WHO grade II: 1.73+/-0.59; WHO grade III: 1.74+/-0.38; WHO grade IV: 1.59+/-0.35, (mean+/-SD, T/B ratios of mean tumour uptake)]. The median survival time of patients with a high T/B ratio on IMT SPET was not significantly different from that of patients with a low T/B ratio (T/B ratio <1.6, 14.8 months; T/B ratio > or =1.6, 13.0 months). Thus, no evidence could be found for a relationship between IMT uptake in cerebral gliomas and either histological grading or survival time. Nevertheless, IMT SPET constitutes a useful method for the detection of primary and recurrent gliomas, determination of tumour extent and individual follow-up.     

T1, T2 and proton density measurements in the grading of cerebral gliomas

The possibility that cerebral tumours may be graded by measuring T1 or T2 with magnetic resonance (MR) imaging was studied. A consecutive series of patients with subsequently verified gliomas was enrolled, and studied with MR. Patients who had prior surgical, chemotherapeutic or steroid treatment were excluded. Single slice multiple saturation recovery and multiple spin echo techniques were used to measure T1, T2 and proton density in the tumour. In 33 patients with cerebral gliomas there were 5 grade I, 12 grade II, 7 grade III and 9 grade IV. T1 and T2 values tended to be smaller in grade I gliomas than in grades II, III and IV gliomas. Relaxation parameters overlapped considerably in tumours with different grades. Proton density values did not show much change between different grades of gliomas. Relaxation parameters cannot be used to determine tumour grade reliably. Correspondence to: S. Newman     

Intra-individual comparison of p-[<Superscript>123</Superscript>I]-iodo-L-phenylalanine and L-3-[<Superscript>123</Superscript>I]-iodo-α-methyl-tyrosine for SPECT imaging of gliomas

Objectives Radioactive amino-acids accumulate in gliomas even with an intact blood-brain-barrier. L-3-[¹²³I]-iodo-α-methyl-tyrosine (IMT) is well established for SPECT imaging of gliomas. Recently, we introduced p-[¹²³I]-iodo-L-phenylalanine (IPA) for the characterisation of brain lesions. This study compares both tracers in glioma patients. Methods Eleven patients with gliomas (1 WHO grade 1, 5 grade 2, 1 grade 3, 2 grade 4 gliomas, 1 unconfirmed upgrading and 1 post-therapeutic non-neoplastic lesion) underwent SPECT imaging with IPA (early and delayed acquisitions at 30 min and 3 h) and IMT (early only). Maximum tumour-to-brain ratios (TBR) were calculated using region-of-interest analysis to assess uptake of IMT and IPA. Imaging results were compared to histopathological findings. Results Early TBRs of IMT and IPA were strongly correlated (r = 0.828, p = 0.002). TBRs were higher for IMT than IPA (1.95±0.50 versus 1.79±0.42; p < 0.05), but independent from tumour cell density (p > 0.1). Visual interpretation by different observers was more concordant for IMT-SPECT than IPA-SPECT (kappa 1.0 versus 0.774). No differences in early TBRs were observed between low-grade and high-grade gliomas for IMT (1.97±0.53 versus 2.21±0.44, p > 0.5) or IPA (1.70±0.23 versus 2.21±0.56, p = 0.167) with a trend to higher TBRs in low-grade tumours for IMT (p = 0.093). In contrast to the known wash-out of IMT, we observed persistent accumulation of IPA in gliomas. Conclusions IPA shows lower TBRs than IMT, especially in low-grade tumours, so IMT should be preferred for the delineation of low-grade gliomas by SPECT imaging. Due to its prolonged retention, however, IPA remains promising for therapeutic use in gliomas after labelling with I-131. This work was supported by a grant from the “Deutsche Krebshilfe” (70-3024-He 1).     

Diagnostic potential of short echo time MR spectroscopy of gliomas with single-voxel and point-resolved spatially localised proton spectroscopy of brain

Accurate neuroimaging grading of gliomas is useful for management, but techniques such as MRI and CT are not sufficiently reliable. Necrosis is a consistent, decisive prognostic factor and the key diagnostic criterion for glioblastoma multiforme. MR spectroscopy (MRS) allows noninvasive measurement of metabolites in brain tumours and mobile lipids reflect necrosis. However, short echo-time (TE) spectroscopy has been required for reliable assessment of lipids, since their relaxation times are very short. Recent advances have made it possible to perform short-TE MRS. We attempted to evaluate the significance of short TE spectroscopy as part of routine imaging for diagnosis and grading of gliomas. We performed TE 30 ms MRS in 25 patients with gliomas (grade II six; grade III three; grade IV, 16) and in 19 areas of healthy white matter using proton brain examination/single voxel (PROBE/SV) and point-resolved spatially localised spectroscopy (PRESS). With short-TE spectroscopy, lipid signals were detected in all 16 tumours of grade IV, one grade II (P = 0.0002) and none of grade III (P = 0.001). TE 136 ms MRS, carried out in 20 of these cases, showed lipid signals in only four of 14 grade IV tumours and in none of the other six. N-acetylaspartate/choline (NAA/Cho) ratios were always more than 1.0 in healthy tissues and less than 1.0 in all but one of the gliomas. The mean creatine (Cr)/Cho ratio in each tumour grade was significantly lower than in the healthy tissues. The mean Cr/Cho ratio was also significantly lower in grade IV than in grade II tumours (P < .0005). Considerable overlap in Cr/Cho ratio was observed between grade II and grades III and IV gliomas at long but less so at short-TE MRS. We conclude that short-TE MRS with PROBE/SV and PRESS is of value in grading gliomas. Received: 25 June 2000 Accepted: 1 September 2000     

Role of diffusion- and perfusion-weighted MR imaging for brain tumour characterisation

Purpose  This study was undertaken to correlate apparent diffusion coefficient (ADC) and relative regional cerebral blood volume (rrCBV) to histological findings in a large series of patients with primary or secondary brain tumours to evaluate diffusion-weighted (DWI) and perfusionweighted (PWI) imaging in the characterisation of cerebral tumors. Materials and methods  Ninety-eight patients with cerebral tumours, 46 of which were primary (seven grade 0-I, nine low-grade gliomas, two gliomatosis cerebri, nine lymphomas and 19 high-grade gliomas) and 52 secondary, underwent conventional magnetic resonance (MR) imaging completed with DWI and dynamic contrast susceptibility PWI. Both ADC and rrCBV were calculated on a workstation by using Functool 2 software. Student’s t test was used to determine any statistically significant differences in the ADC and rrCBV values. Results  Seventeen of 98 tumours were cystic or necrotic (12/17 hypointense and 5/17 hyperintense on DWI); the ADC value of hyperintense cystic areas was 0.97±0.23×10⁻³ mm²/s. The ADC value of solid tumours varied between 0.64 and 3.5×10⁻³ mm²/s. The rrCBV value was 1.4 (σ 0.66) in low-grade gliomas; 1.22 (σ 0.25) in lymphomas; 4.5 (σ 0.85) in grade III gliomas; 3.18 (σ 1.26) in grade IV gliomas and 2.53 (σ 1.6) in metastases. Conclusions  DWI has an important role in the differential diagnosis of cystic cerebral masses but not in tumour characterisation. PWI is helpful in differentiating high-from low-grade gliomas and lymphomas from high-grade gliomas.      

Epithelial and stromal metabolite changes in the transition from cervical intraepithelial neoplasia to cervical cancer: an in vivo 1H magnetic resonance spectroscopic imaging study with ex vivo correlation

To investigate epithelial and stromal metabolite changes in cervical intraepithelial neoplasia (CIN) and cervical cancer in vivo and correlate findings with MR spectroscopy of tissue samples. Forty-seven women (19 with CIN, 28 with cervical cancer) underwent endovaginal MR at 1.5 T with T2-W and localised 2D MR spectroscopic imaging (PRESS, TR = 1,500 ms, TE = 135 ms). tCho, 2 ppm and -CH₂ lipid peaks were measured in epithelial (>50% epithelium, no tumour), stromal (>50% stroma, no tumour) and tumour (>30% tumour) voxels. Unsuppressed water signal from the same voxel provided a concentration reference. ¹H HR-MAS MR spectra were acquired from tissue in 37 patients (11.74 T, pulse-acquire and cpmg sequences, with water pre-saturation). Analysable data from 17 CIN and 25 cancer patients showed significant increases in tCho (p = 0.03) and 2 ppm (p = 0.007) in tumour compared with epithelial voxels from CIN patients, but not with epithelial voxels from cancer patients. No significant differences were seen in stroma from cancer compared with CIN patients. Differences in -CH₂ lipids were not significant between groups. There was no significant correlation between in vivo and ex vivo tCho or -CH₂ lipids. Estimated in vivo concentrations of tCho and 2 ppm resonances increase in tumour and adjacent epithelium in progression from CIN to cervical cancer. This work was supported by Cancer Research UK (CUK) grant nos. C1353/A5408 and C1060/A808.     

Low-grade (WHO II) and anaplastic (WHO III) gliomas: differences in morphology and MRI signal intensities

Objective

To evaluate the diagnostic potential of a multi-factor analysis of morphometric parameters and signal characteristics of brain tumours and peritumoural areas for distinguishing WHO-grade II and III gliomas at magnetic resonance imaging (MRI).

Methods

MR examinations of 108 patients with histologically proven World Health Organization (WHO) grade II and III gliomas were included. Morphological criteria and MR signal characteristics were evaluated. The data were subjected to a multifactorial logistic regression analysis to differentiate between grade II and grade III gliomas. The discriminatory power was assessed by receiver operating characteristic (ROC).

Results

Logistic regression analysis showed that WHO grade II and III can be distinguished based on contrast enhancement, cortical involvement, margin of the enhancing lesion and maximum diameter (width and length) of the peritumoural area (the so-called tumour infiltration zone). With the final model of logistic regression analysis and with the cut-off value?≥?0.377, WHO grade III glioma is predicted with a sensitivity of 71.0 % and a specificity of 80.4 %.

Conclusion

Measurement of maximum diameter of peritumoural area, contrast enhancement as well as cortical involvement and the margin of the contrast-enhancing lesion can be used easily in clinical routine to adequately distinguish WHO grade II from grade III gliomas.

Key Points

? MRI offers new information concerning WHO-grade II and III gliomas. ? The differentiation between such tumour grades is important for therapeutic decisions. ? We assessed differences in enhancement, cortical involvement, margins and peritumoural appearances. ? WHO grade III gliomas can be predicted with reasonable sensitivity and specificity.     

Evaluation of l-3-[123I]iodo-α-methyltyrosine SPET and [18F]fluorodeoxyglucose PET in the detection and grading of recurrences in patients pretreated for gliomas at follow-up: a comparative study with stereotactic biopsy

. Based on the results of stereotactic biopsy, we evaluated in a prospective fashion the efficiency of l-3-[¹²³I]iodo-α-methyltyrosine-single-photon emission tomography (SPET) and [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in the detection and grading of recurrences in patients previously treated for gliomas. The patient population comprised 30 individuals, nine with astrocytomas of grade II, ten with astrocytomas of grade IV, three with oligoastrocytomas of grade II, six with oligodendrogliomas of grade II and two with anaplastic oligodendrogliomas of grade III) suspected of recurrence and scheduled for further treatment. IMT SPET data were acquired using either by dual-or a triple-headed SPET camera, Multispect 2/3. FDG uptake was measured with an ECAT ART PET camera. Two independent observers classified PET and SPET images as positive or negative for tumour tissue. Uptake of FDG and IMT was evaluated visually and, in the case of IMT, also quantitatively by calculating the ratios between tracer accumulation in the lesion and the unaffected contralateral regions of reference using the region of interest (ROI) technique. The PET and SPET results were compared with the histopathological findings obtained either by stereotactic biopsy or in one case by open surgery. Glucose metabolism and amino acid uptake of recurrences of brain tumours as assessed by FDG-PET and IMT-SPET correlated highly with the histopathological findings. Based on the histopathological data, FDG-PET and IMT-SPET findings confirmed recurrence in all cases of high-grade gliomas (IV). A difference could be demonstrated in low-grade (II–III) tumour recurrences. True-positive IMT-SPET results were found in 86% of grade III and 75% of grade II recurrences, whereas FDG-PET yielded a sensitivity of 71% in tumours of grade III and 50% in those of grade II. With respect to the grade of malignancy of brain tumours at recurrence, IMT-SPET, in contrast to FDG-PET, does not permit adequate in vivo grading of non-mixed brain tumours of astrocytic or oligodendroglial origin. However, in this study FDG-PET did not permit discrimination between upgrading of low-grade oligoastrocytomas (II) into anaplastic oligodendrogliomas (III) and upgrading into glioblastomas (IV) The results of this study indicate that FDG-PET and IMT-SPET are equivalent to stereotactic biopsy in their ability to identify high-grade tumours at recurrence. IMT-SPET proved to be superior to FDG-PET in confirming low-grade recurrences. In the case of suspected progression of the grade of malignancy in ordinary gliomas, FDG-PET correlated significantly with the histopathological grading, whereas IMT-SPET did not. However, tumour grading by FDG-PET has a limitation in mixed brain tumours in that it is not possible to discriminate between progression of the oligo- versus the astrocytic tumour entity. In this case histopathological evaluation of the tumour grade remains necessary. Received 6 August and in revised form 2 November 1998     

Gray matter-white matter contrast on spin-echo T1-weighted images at 3 T and 1.5 T: a quantitative comparison study

Discrepancies exist in the literature regarding contrast between gray and white matter on spin-echo (SE) T1-weighted MR imaging at 3 T. The present study quantitatively assessed differences in gray matter-white matter contrast on both single- and multi-slice SE T1-weighted imaging between 3 and 1.5 T. SE T1-weighted sequences with the same parameters at both 3 and 1.5 T were used. Contrast-to-noise ratio (CNR) between gray and white matter (CNR_GM-WM) was evaluated for both frontal lobes. To assess the effects of interslice gap, multi-slice images were obtained with both 0 and 25% interslice gap. Single-slice CNR_GM-WM was higher at 3 T (17.66 ± 2.68) than at 1.5 T (13.09 ± 2.35; P < 0.001). No significant difference in CNR_GM-WM of multi-slice images with 0% gap was noted between 3 and 1.5 T (3T, 8.61 ± 2.55; 1.5T, 7.43 ± 1.20; P > 0.05). Multi-slice CNR_GM-WM with 25% gap was higher at 3T (12.47 ± 3.31) than at 1.5 T (9.73 ± 1.37; P < 0.001). CNR_GM-WM reduction rate of multi-slice images with 0% gap compared with single-slice images was higher at 3T (0.47 ± 0.13) than at 1.5 T (0.38 ± 0.09; P = 0.02). CNR_GM-WM on single-slice SE T1-weighted imaging and CNR_GM-WM on multi-slice images with 25% interslice gap were better at 3 T than at 1.5 T. The influence of multi-slice imaging on CNR_GM-WM was significantly larger at 3T than at 1.5 T. This study was supported in part by a Health and Labour Sciences Research Grant of Japan Yasutaka Fushimi and Yukio Miki equally contributed to the study.     

Tumour hypoxia imaging with [18F]FAZA PET in head and neck cancer patients: a pilot study

Purpose Hypoxia is an important negative prognostic factor for radiation treatment of head and neck cancer. This study was performed to evaluate the feasibility of use of ¹⁸F-labelled fluoroazomycin arabinoside ([¹⁸F]FAZA) for clinical PET imaging of tumour hypoxia. Methods Eleven patients (age 59.6 ± 9 years) with untreated advanced head and neck cancer were included. After injection of approximately 300 MBq of [¹⁸F]FAZA, a dynamic sequence up to 60 min was acquired on an ECAT HR+ PET scanner. In addition, approximately 2 and 4 h p.i., static whole-body PET (n = 5) or PET/CT (n = 6) imaging was performed. PET data were reconstructed iteratively (OSEM) and fused with CT images (either an external CT or the CT of integrated PET/CT). Standardised uptake values (SUVs) and tumour-to-muscle (T/M) ratios were calculated in tumour and normal tissues. Also, the tumour volume displaying a T/M ratio >1.5 was determined. Results Within the first 60 min of the dynamic sequence, the T/M ratio generally decreased, while generally increasing at later time points. At 2 h p.i., the tumour SUV_max and SUV_mean were found to be 2.3 ± 0.5 (range 1.5–3.4) and 1.4 ± 0.3 (range 1.0–2.1), respectively. The mean T/M ratio at 2 h p.i. was 2.0 ± 0.3 (range 1.6–2.4). The tumour volume displaying a T/M ratio above 1.5 was highly variable. At 2 h p.i., [¹⁸F]FAZA organ distribution was determined as follows: kidney > gallbladder > liver > tumour > muscle > bone > brain > lung. Conclusion [¹⁸F]FAZA PET imaging appears feasible in head and neck cancer patients, and the achieved image quality is adequate for clinical purposes. Based on our initial results, [¹⁸F]FAZA warrants further evaluation as a hypoxia PET tracer for imaging of cancer.     

Differences in complication rates among the centres in the SPACE study

Introduction  Despite the high grade of standardisation of study protocols, there is still room for variability among the centres in specific treatment aspects. We evaluated the treatment risk in stent-protected angioplasty of the carotid versus endarterectomy (SPACE) associated with the specific patient enrolment rates of the centres. Materials and methods  The analysed endpoints were ipsilateral stroke or death [primary outcome event (pOE)] and any stroke or death [secondary outcome event (sOE)] until 30 days after treatment. A binary logistic regression analysis with random effects was performed separately for each treatment arm. The centres were secondarily categorised in three classes: I) ≥25 patients enrolled, II) ten to 24 patients and III) <10 patients and a hierarchic log linear model was fitted to test the three-way interaction of treatment, number of patients per class and outcome. Results  The random effects logistic regression analysis in the carotid artery stenting (CAS) arm proved a significant increase in pOE with decreasing number of patients enrolled (−0.0190 ± 0.0085, p = 0.025, deviance 35.7 with 32 df), whereas no such effect was found in the carotid endartectomy (CEA) arm (−0.010 ± 0.008, p = 0.24, deviance 39.78 with 32 df). In the log linear model, there was a significant interaction between treatment, number of patients per centre and sOE (p = 0.023). The odds ratios for sOE in the enrolment classes (CAS vs. CEA) were 0.98 (95% CI 0.50–1.94, p = 0.95) for class I, 1.13 (95% CI 0.47–2.77, p = 0.77) for class II and 11.56 (95% CI 1.40–253.45, p = 0.01) for class III centres. Conclusion  Despite rigorous standardisation and quality requirements for operator qualification, there seemed to be a decrease in complication rate with increasing patient enrolment numbers in the CAS arm while this signal could not be detected in the CEA arm of SPACE.     

Optimizing multidetector CT for visualization of splenic vascular injury. Validation by splenic arteriography in blunt abdominal trauma patients

Nonoperative management of blunt splenic injury is the treatment of choice in hemodynamically stable patients. Detection of vascular injury by multidetector CT (MDCT) is the most significant factor predicting the need for endovascular treatment. This study evaluated the timing of the appearance of vascular lesions during angiography. Images from 20 patients embolized for pseudoaneurysms (PSA) were evaluated. Angiograms were reviewed for phase and timing of PSA. Admission MDCT was reviewed for injury grade and PSA. Initial MDCT evaluation indicated grade III and IV splenic injuries in 9 and 11 patients, respectively. PSA was seen on MDCT in 14/20 (70%) patients. Time from opacification of the aorta to vascular injury was 1.32 s for arterial phase injuries compared with 2.05 s for postcapillary injuries (P = 0.097). Angiography demonstrated 15 vascular injuries during the arterial and 5 in the venous phase. Of injuries seen during arterial phase angiography, 10/15 (66%) were identified on MDCT. Of the five injuries that exhibited postcapillary-phase findings, 4/5 (80%) demonstrated PSA (P = 0.5). Vascular lesions are a better indicator of subsequent clinical deterioration than splenic injury grade. PSAs are more frequently seen in postcapillary vascular injuries than arterial phase lesions with the current timing of MDCT. In a subset of patients in whom splenic injury grades III and IV warrant angiography, PSAs are not initially demonstrated on MDCT. Therefore, alteration of MDCT timing parameters to better correlate with arterial phase angiography may improve initial diagnosis of vascular injury.     

Radioembolisation with <Superscript>90</Superscript>Y-microspheres: dosimetric and radiobiological investigation for multi-cycle treatment

Introduction  Radioembolisation with ⁹⁰Y-microspheres is a new locoregional treatment of hepatic lesions, usually applied as single cycle. Multi-cycle treatments might be considered as a strategy to improve the risk-benefit balance. With the aim to derive suitable information for patient tailored therapy, available patients’ dosimetric data were reviewed according to the linear–quadratic model and converted into biological effective dose (BED) values. Single vs. multi-cycle approaches were compared through radiobiological perspective. Materials and methods  Twenty patients with metastatic lesions underwent radioembolisation. The ⁹⁰Y-administered activity (AA) was established in order to respect a precautionary limit dose (40 Gy) for the non-tumoral liver (NTL). BED was calculated setting α/β = 2.5 Gy (NTL), 10 Gy (tumours); T _1/2,eff = T _1/2,phys = 64.2 h; T _1/2,rep = 2.5 h (NTL), 1.5 h (tumours). The BED to NTL was considered as a constraint for multi-cycle approach. The AA for two cycles and the percent variations of AA, tumour dose, BED were estimated. Results  In one-cycle, for a prescribed BED to NTL of 64 Gy (NTL dose = 40 Gy), AA was 1.7 (0.9–3.2) GBq, tumour dose was 130 (65–235) Gy, and tumour BED was 170 (75–360) Gy. Considering two cycles, ∼15% increase was found for AA and dose to NTL, with unvaried BED for NTL. Tumour dose increase was 20 (10–35) Gy; tumour BED increase was 10 (3–11) Gy. In different protocols allowing 80 Gy to NTL, the BED sparing estimated was ∼50 Gy (two cycles) and 65 Gy (three cycles). Conclusions  From a radiobiological perspective, multi-cycle treatments would allow administering higher activities with increased tumour irradiation and preserved radiation effects on NTL. Trials comparing single vs. multiple cycles are suggested.     

Standardized uptake value in para-aortic lymph nodes is a significant prognostic factor in patients with primary advanced squamous cervical cancer

Purpose We sought to identify prognostic factors—including positron emission tomography (PET) parameters—in patients with previously untreated squamous carcinoma of the uterine cervix and MRI- or CT-defined pelvic or para-aortic lymph node (PLN or PALN) metastasis. Materials and methods Patients with untreated squamous cell cervical cancer and PLN or PALN metastasis detected by CT/MRI were enrolled. FDG-PET scans were performed for primary staging. Prognostic variables were investigated by univariate and multivariate analyses. Five-year recurrence-free and 5-year overall survivals (RFS and OS) were evaluated using the Kaplan–Meier method. Results A total of 70 patients [54 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I or II, and 16 patients with stage III or IV] were eligible. Follow-up ranged from 26.1 to 71.6 months. In multivariate analysis, FIGO stage ≥III (5-year RFS, p = 0.008; 5-year OS, p = 0.008) was a significant prognostic factor for both RFS and OS. In addition, SUV_max for PALN (dichotomized by 3.3) was significantly associated with OS (p = 0.012) and marginally with RFS (p = 0.078). The presence of SUV_max ≥ 3.3 at PALN or FIGO stage ≥III were significantly associated with both recurrence [5-year RFS; HR = 4.52, 95% confidence interval (CI) = 1.73–11.80] and death (5-year OS; HR = 6.04, 95% CI = 1.97–18.57). Conclusion SUV_max ≥ 3.3 for PALN and FIGO stage ≥III were significant adverse factors in patients with primary squamous cervical carcinoma and PLN or PALN metastasis detected by CT/MRI. This study was presented in part at the 42nd American Society of Clinical Oncology Annual Meeting, 2006, Atlanta, GA, USA.     

Perfusion characteristics of late radiation injury of parotid glands: quantitative evaluation with dynamic contrast-enhanced MRI

We aimed to quantitatively investigate the alteration of parotid perfusion after irradiation using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on a two-compartment tracer kinetic model. This study enrolled 19 patients (53.2 ± 14.9 years) treated by head and neck radiotherapy and 19 age-relevant and sex-matched subjects as a control group. Perfusion parameters (K _el , k ₂₁ and A) of parotid glands were analyzed based on the Brix model from T1-weighted DCE-MRI. Suitability of the Brix model was evaluated via Monte Carlo simulation for the goodness-of-fit. Analysis of nonlinear goodness-of-fit showed that the Brix model is appropriate in evaluating the parotid perfusion (R² = 0.938 ± 0.050). The irradiated parotid glands showed significantly lower K _el (P < 0.0005) and k ₂₁ (P < 0.05) and consequently significantly higher value of peak enhancement (P < 0.0005) and time-to-peak (P < 0.0005) compared with non-irradiated ones, suggestive of gradual and prolonged accumulation and delayed wash-out of contrast agent due to increased extracellular extravascular space and decreased vascular permeability in the irradiated glands. Linear regression analysis showed dose-dependent perfusion changes of the irradiated parotid glands. We conclude that quantitative DCE-MRI is a potential tool in investigating parotid gland perfusion changes after radiotherapy.     

Correlation of volume transfer coefficient Ktrans with histopathologic grades of gliomas

Purpose:

To evaluate the roles of dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) and optimum tracer kinetic parameters in the noninvasive grading of the glial brain tumors with histopathological grades (I–IV).

Materials and Methods:

Twenty‐eight patients with histopathologically graded gliomas were imaged. Images with five flip angles were acquired before injection of gadolinium‐DTPA and were processed to calculate the T₁ value of each region of interest (ROI). All the DCE‐MRI data acquired during the injection were processed based on the MRI signal and pharmacokinetic models to establish concentration–time curves in the ROIs drawn within the tumors, contralateral normal areas, and area of the individual artery input functions (iAIF) of each patient. A nonlinear least‐square‐fitting method was used to obtain tracer kinetic parameters. Kruskal–Wallis H‐test and Mann–Whitney U‐test were applied to these parameters in different histopathological grade groups for statistical differences (P < 0.05).

Results:

Volume transfer coefficient (K^trans) and extravascular extracellular space volume fraction (V_e) calculated using iAIFs can be used not only to distinguish the low (ie, I and II) from the high (ie, III and IV) grade gliomas (P() < 0.001 and P_Ve < 0.001), but also grade II from III (P() = 0.016 and P_Ve = 0.033).

Conclusion:

K^trans is the most sensitive and specific parameter in noninvasive grading, distinguishing the high (III and IV) from the low (I and II) grade and high grade III from low grade II gliomas. J. Magn. Reson. Imaging 2012;36:355–363. © 2012 Wiley Periodicals, Inc.