Initial experience with Tc-99m-HM-PAO in the study of brain tumors

A preliminary study of the distribution of the ^99mTc complex of hexamethylpropylene amine oxime (HM-PAO) in 12 patients with brain neoplasms before, during, and after radiotherapy has been performed. Untreated brain tumors were found to exhibit a range of ^99mTc-HM-PAO uptake, varying from areas of markedly increased isotope activity to photopenic areas, when compared to normal brain tissue. A ratio of ^99mTc-HM-PAO tumor uptake to contralateral normal tissue uptake was calculated prior to and during radiotherapy. This ratio tended to return towards unity in lesions responding to therapy. A predictable alteration in whole brain ^99mTc-HM-PAO uptake during radiotherapy was not demonstrated. Unlike the radiolabeled amines, ^99mTc-HM-PAO localizes in primary tumors, probably indicating that its uptake mechanism is independent of non specific amine receptors. ^99mTc-HM-PAO may be useful in the study of brain tumor physiology and response to therapy.     

MR imaging of the brain: tumors

The radiologic modality that most likely provides the imaging information needed in a patient suspected of having a brain tumor is MR imaging. A brain tumor can be reliably ruled out if the MR examination is performed properly and experts interpret the results as negative. If there is a tumor, however, its exact location and topography must be determined. Important for therapy and prognosis are also tumor properties such as histologic type and grade, as well as effects on adjacent brain structures. Although potentially a noninvasive method of in vivo neuropathology, MR is still far from being sufficiently specific, as dissimilar lesions may look the same despite the use of refined imaging protocols. The evolution of MR imaging continues, however, making further methodologic improvement likely. Presently, advanced methods, such as diffusion- and perfusion-weighted MR imaging, functional MR imaging, neuronavigation based on MR imaging data, and the use of MR imaging during surgery (intraoperative MR imaging), influence the way patients are treated. Likewise, follow-up imaging (monitoring) of tumor patients by MR has become more effective, and experience has shown how to distinguish reactive changes from recurrent tumor. In the future, MR imaging may gain importance in the development of novel therapeutic concepts.     

MRS of brain tumors: Diagrammatic representations and diagnostic approach

Purpose

To evaluate magnetic resonance spectroscopy (MRS) in the assessment of brain tumors and grading brain glioma.

Patients and methods

Retrospective study was done for 42 patients with diagrammatic representations suggested by the author for the assessment of MRS data.

Results

Pathology grading was correlated with metabolic ratios in cases of brain glioma. Ratios higher than 1.5 for either Cho/Cr or Cho/NAA were consistent with tumors and ratios higher than 2 were consistent with high grade glioma or metastases.

Conclusion

MRS can be used to grade cases of brain glioma. Diagrammatic representations and a diagnostic approach were suggested by the author to simplify clinical practice.     

Language and memory lateralization and localization using different fMRI paradigms in Arabic speaking patients: Initial experience

Purpose

Presurgical assessment of memory in patients with temporal lesions is essential to evaluate the effect of treatment on cognitive functioning (1). In recent years, there has been an increasing interest in the utility of functional MR imaging (fMRI) for presurgical evaluation of memory (2). There is no established fMRI protocol to evaluate memory functions presurgically (3). The identification of language areas in patients undergoing brain surgery is a major clinical challenge, the gold standard for the identification of essential language areas in neurosurgical patients is intraoperative mapping (IOM) by direct cortical stimulation as used by various groups but other techniques, such as functional imaging, are rapidly evolving (4). Language and also memory paradigms designed for patients speaking languages other than Arabic are not totally applicable for examining Arabic speaking and illiterate patients except after some modifications, the aim of this study is to test the applicability of these modified western designed paradigms for lateralization and localization of cortical brain centres concerned with language and memory in Arabic speaking patients.

Materials and methods

Using a 1.5 T Philips scanner, multiple modified western designed language and memory fMRI paradigms were used to assess the eloquent cortical brain areas in Arabic speaking patients of different levels of education having different lesions mainly brain tumors and epilepsy. These modifications consist mainly of providing simpler paradigms in an easy common Arabic language not in high level traditional Arabic, choosing simplified topics for the less educated patients, avoiding any written paradigms and depending on auditory paradigms in easy common Arabic language and simple pictures for illiterate patients. Images were analyzed using Philips extended MR work space release 2.5.3.0. The results were analyzed and compared to each other as regarding the patient cooperation and the ability to give robust fMRI signal.

Results

Multiple fMRI paradigms are efficient in lateralization and localization of cortical centres of language and memory yet they are variable in their ability to give robust fMRI signal clusters, also patients with different levels of education and culture differ in their ability to cooperate with the fMRI paradigms thus also affects the results.

Conclusion

Language and memory fMRI paradigms reported in the western literature are applicable to Arabic speaking patients with brain lesions undergoing an fMRI exam for language and/or memory but need some modifications according to background and level of education to get more robust identification of eloquent language and memory cortical centres.     

MR spectroscopy in post-treatment follow up of brain tumors

PurposeTo detect the role of MR spectroscopy in evaluating the whole area of signal alteration within the irradiated volume aiming to differentiate recurrent/residual tumors from radiation injury and to detect the tumor margin and extent.Materials and methodsThis prospective study included 25 patients with previously treated primary intracranial tumors. All patients received radiotherapy. MRI and multivoxel MRS were performed. The volume of interest was placed over the whole area of signal alteration. The spectra were analyzed for the signal intensity of choline (Cho), creatine (Cr), and N-acetyl aspartate (NAA), lipid (Lip), lactate (Lac), and myo-inositol (mI). Metabolite ratios for Cho/NAA, Cho/Cr, and NAA/Cr were calculated.ResultsCho/NAA and Cho/Cr were significantly higher while NAA/Cr ratios were significantly lower in tumors than radiation injury (p = 0.001 for all ratios). The Cho/NAA and Cho/Cr ratios were significantly higher in radiation injury than in normal-appearing brain tissue (p = 0.032 and p = 0.008, respectively), whereas NAA/Cr was insignificantly lower in radiation injury than normal-appearing brain tissue (p = 0.051). Value >1.8 for Cho/NAA ratio was considered as indicator for tumor.ConclusionMR spectroscopy can differentiate recurrent/residual tumor from radiation injury and delineate the tumor margin and extent.     

不同时辰针刺足少阴肾经脑功能磁共振成像对比研究

目的:探讨不同时辰针刺足少阴肾经后引起的脑功能变化及其各功能区在脑内定位的异同和分布规律,寻找不同时辰针刺同一经络治疗效果差异的中枢原因。方法:健康志愿者20例在足少阴肾经开穴和闭穴时配伍电针针刺太溪与复溜两穴位后进行磁共振脑功能成像实验,同时选取2个非穴位针刺点进行同样的实验作为对照。结果:足少阴肾经开穴组与闭穴组脑功能成像结果显示功能被激活信号增高和功能被抑制信号减低的脑区有不同。开穴组最大激活脑区位于双侧扣带回,最大抑制脑区位于右侧眶内侧回。闭穴组最大激活脑区位于左侧小脑,最大抑制脑区位于右侧眶内侧回。结论:脑功能磁共振成像观察到的不同时辰针刺后中枢效应的差异,不同时辰针刺非穴点后,没有这种差异。不同时辰针刺足少阴肾经后,脑功能激活信号增高脑区和信号减低抑制脑区均有差异,开穴时段内两经络激活区和抑制区的数目和范围要比闭穴时段内多和广。开穴时可以形成完整的中枢激活与反射环路,闭穴时则无法形成完整的环路。     

Uptake of 11C-l-and d-methionine in brain tumors

¹¹C-labeled l-and d-methionine uptake was measured in seven patients with brain tumors using positron emission tomography. Tumors accumulated both isomers of the tracer. The strongest uptake occurred in tumors with a high grade of malignancy, while low grade tumors accumulated less activity. The l to d uptake ratio in tumor regions ranged from 0.92–1.25. Conventional ^99mTc-DTPA scans revealed blood-brain barrier damage in two patients with no or only slight ¹¹C-methionine accumulation, while one patient with a negative ^99mTc-DTPA scan accumulated ¹¹C-methionine in the tumor region. In view of the biochemical pathway of methionine and the present findings, it is concluded that the uptake reflects metabolic activity in brain tissue rather than uptake by diffusion due to disruption of the blood-brain barrier.     

Volume MRI and MRSI techniques for the quantitation of treatment response in brain tumors: Presentation of a detailed case study

Patients with primary brain tumors may be considered for several different treatments during the course of their disease. Assessments of disease progression and response to therapy are typically performed by visual interpretation of serial MRI examinations. Although such examinations provide useful morphologic information, they are unable to reliably distinguish active tumor from radiation necrosis. This poses a particular problem in the assessment of response to localized radiation therapies such as gamma knife radiosurgery. In this paper, we present methodology for evaluating changes in tissue morphology and metabolism based on serial volumetric MRI and magnetic resonance spectroscopic imaging (MRSI) examinations. Registration and quantitative analysis of these data provide measurements of the temporal and spatial distributions of gadolinium enhancement and of N-acetylasparate, choline, creatine, and lactate/lipid. The key features of this approach and the potential clinical benefits are illustrated by a detailed analysis of six serial MRI/MRSI examinations and three serial 1-[F-18] fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) studies on a patient with a recurrent anaplastic astrocytoma.     

The use of a partial transmission shield to reduce the optic chiasm doses during radiation therapy treatment of brain tumors

Historically, brain tumors have been treated with lateral opposed beams for 40–45 Gy followed by more conformal reduced fields. Advances in treatment planning computers have led to the implementation of conformal non-axial techniques, allowing for escalation of dose. In patients where total doses exceed 50 Gy, adjacent critical structures can be protected with a partially shielded transmission block over the optic nerves and chiasm. By eliminating the conedown portion of the treatment a more cost and time effective treatment is achieved. Partially shielded blocks can be designed by using cerrobend or multileaf collimation. They can be included in the treatment plan and verified by an irregular field calculation and/or thermoluminescent dosimeters.     

Outcomes of embolization of bone tumors in the pelvic and shoulder girdles: Initial experience

Purpose

To assess the effectiveness of transarterial embolization of bone tumors as preoperative technique to reduce blood loss or as a curative method in bone tumors of shoulder and pelvic girdles.

Proton magnetic spectroscopic imaging of the child's brain: the response of tumors to treatment

Our aim was to determine and/or predict response to treatment of brain tumors in children using proton magnetic resonance spectro-scopic imaging (MRSI). We studied 24 patients aged 10 months to 24 years, using MRI and point-resolved spectroscopy (PRESS; TR 2000 TE 65 ms) with volume preselection and phase-encoding in two dimensions on a 1.5 T imager. Multiple logistic regression was used to establish independent predictors of active tumor growth. Biologically vital cell metabolites, such as N-acetyl aspartate and choline-containing compounds (Cho), were significantly different between tumor and control tissues (P < 0.001). The eight brain tumors which responded to radiation or chemotherapy, exhibited lower Cho (P = 0.05), higher total creatine (tCr) (P = 0.02) and lower lactate and lipid (L) (P = 0.04) than 16 tumors which were not treated (except by surgery) or did not respond to treatment. The only significant independent predictor of active tumor growth was tCr (P < 0.01). We suggest that tCr is useful in assessing response of brain tumors to treatment.     

Echo-planar magnetic resonance imaging (EPI) with high-resolution matrix in intra-axial brain tumors

The aim of this study was to assess the potential of high-speed interleaved echo-planar imaging (EPI) to achieve diagnostic image quality comparable to T2-weighted imaging in patients with brain tumors. Seventeen patients with intra-axial, supratentorial tumors (10 untreated gliomas, 7 radiated gliomas) were investigated on a 1.5-T scanner. The conventional scan (SE, TR/TE = 2200/80 ms, 18 slices) was acquired in 8 min, 4 s, and EPI (TR/TE = 3000/80 ms, 18 slices) was completed in 25 s. The films were compared in a blinded trail by three radiologists. On the general impression and anatomic display, both sequences were rated to be of similar quality. Artifacts were slightly more pronounced at the skull base and around surgical clips using EPI. Tumor delineation was nearly equivalent using EPI, compared with the T2-weighted sequence. Echo-planar imaging reached diagnostic quality in all patients. Interleaved high-resolution EPI yielded sufficient quality to depict intra-axial, supratentorial brain tumors. Since EPI can be obtained in a small fraction of the time needed for conventional spin echo, in addition to other indications it could be considered to study patients unable to cooperate. Received: 7 September 1998; Revision received: 6 November 1998; Accepted: 24 November 1998     

Fetal brain tumors: Prenatal diagnosis by ultrasound and magnetic resonance imaging

Congenital central nervous system tumors diagnosed during pregnancy are rare, and often have a poor prognosis. The most frequent type is the teratoma. Use of ultrasound and magnetic resonance image allows the suspicion of brain tumors during pregnancy. However, the definitive diagnosis is only confirmed after birth by histology. The purpose of this mini-review article is to describe the general clinical aspects of intracranial tumors and describe the main fetal brain tumors.     

Influence of brain tumors on the MR spectra of healthy brain tissue

The neurochemical environment of nontumorous white matter tissue was investigated in 135 single voxel spectra of “healthy” white matter regions of 43 tumor patients and 129 spectra of 52 healthy subjects. Spectra were acquired with short TE and TR values. With the data of tumor patients, it was examined whether differences were caused by the tumor itself or aggressive tumor therapies as confounding factors. Comparing the spectra of both classes, an excellent differentiation was possible based on the metabolite peak of N‐acetylaspartate (P ≈ 0) and myoinositol (P < 0.03). The area under curve of the receiver operating characteristic was calculated as 0.86 and 0.62, respectively. With linear discriminant analysis using combinations of integrals, a prediction was possible, whether a spectrum belonged to the patient or the healthy subject class with an overall accuracy above 80%. The confounding factors could be ruled out as source of the differences. The results show strong evidence for an influence of malignant growth on the biochemical environment of nontumorous white matter tissue. Because of the T₁ weighting, the measured differences between both classes were most likely concentration changes interfered by T₁ effects. The underlying processes will be subject of future studies. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Localized 2D J-resolved H MR spectroscopy of human brain tumors in vivo

Application of two-dimensional (2D) J-resolved MR spectroscopy, fully localized in three dimensions to monitor the metabolites in human brain tumors in vivo on a whole body MR scanner is presented. A modified PRESS sequence with [90° – 180° – t₁/2 – 180° – t₁/2-acquisition] was used for voxel localization (2D J point-resolved spectroscopy [PRESS]); chemical shift selective (CHESS) sequence was used for suppression of water. The incremental delay (t₁/2) added to the intervals before and after the last slice-selective 180° RF pulse allowed the monitoring of the J-evolution in a localized 2D NMR spectrum. The addition of the second frequency dimension in 2D J-resolved spectroscopy to encode the indirect spin-spin coupling allowed the visualization of lactate peaks not observed in the 1D MR spectrum because of severe overlap with lipid peaks. 2D spectra of a two-layer phantom with 100 mM alanine and corn oil and also from three patients with tumors are presented here. The 2D spectra show that the J-coupled lactate peaks could be separated even when the lipids peaks severely overlap.     

FLAIR lesion segmentation: Application in patients with brain tumors and acute ischemic stroke

Background

Lesion size in fluid attenuation inversion recovery (FLAIR) images is an important clinical parameter for patient assessment and follow-up. Although manual delineation of lesion areas considered as ground truth, it is time-consuming, highly user-dependent and difficult to perform in areas of indistinct borders. In this study, an automatic methodology for FLAIR lesion segmentation is proposed, and its application in patients with brain tumors undergoing therapy; and in patients following stroke is demonstrated.

Materials and methods

FLAIR lesion segmentation was performed in 57 magnetic resonance imaging (MRI) data sets obtained from 44 patients: 28 patients with primary brain tumors; 5 patients with recurrent-progressive glioblastoma (rGB) who were scanned longitudinally during anti-angiogenic therapy (18 MRI scans); and 11 patients following ischemic stroke.

Results

FLAIR lesion segmentation was obtained in all patients. When compared to manual delineation, a high visual similarity was observed, with an absolute relative volume difference of 16.80% and 20.96% and a volumetric overlap error of 24.87% and 27.50% obtained for two raters: accepted values for automatic methods. Quantitative measurements of the segmented lesion volumes were in line with qualitative radiological assessment in four patients who received anti-anogiogenic drugs. In stroke patients the proposed methodology enabled identification of the ischemic lesion and differentiation from other FLAIR hyperintense areas, such as pre-existing disease.

Conclusion

This study proposed a replicable methodology for FLAIR lesion detection and quantification and for discrimination between lesion of interest and pre-existing disease. Results from this study show the wide clinical applications of this methodology in research and clinical practice.     

健侧顶叶皮层参与卒中急性期脑功能重组:fMRI研究

目的利用功能性磁共振成像(fMRI)技术探讨缺血性卒中急性期的脑功能重组特点。资料与方法采用被动单指运动任务,对4例急性皮质下梗死患者和4名正常人进行fMRI研究,比较正常人与卒中患者之问以及每个卒中患者之问fMRI结果的异同。结果正常人被动单指运动激活对侧感觉运动皮层(SMC)、后顶叶皮层(PPC)和双侧辅助运动区(SMA)。卒中患者健手运动fMRI结果基本同正常人;患手运动时,除1例同(健)侧SMC、SMA、前运动皮层(PMC)激活外,4例均呈现出同侧PPC的激活。结论首次应用fMRI技术采用恒定的被动刺激探讨卒中急性期患者运动恢复的神经机制,结果显示了正常人和脑卒中患者之间fMRI结果的显著差异,反映了卒中急性期脑功能的重组情况,也为卒中急性期健侧半球PPC中介运动恢复提供了新的实验依据。     

Dynamic imaging of intracranial lesions using fast spin-echo imaging: Differentiation of brain tumors and treatment effects

The purpose of this study was to develop a technique for differentiating between recurrent brain tumors and treatment-related changes, such as radiation necrosis, using dynamic MRI. Ninety-five patients with intracranial mass lesions were evaluated using T1-weighted fast spin-echo (FSE) MRI at 1.5 T. Pathologies included treatment-related changes (n = 32), primary tumors (n = 41), metastatic tumors (n = 5), meningiomas (n = 4), and mixed primary/treatment related changes (n = 13). Signal enhancement-time curves were analyzed by fitting to a sigmoidal-exponential function. Maximal enhancement rates were calculated as the first derivative of the fitted curve. Based on the maximal enhancement rates, treatment-related changes could be differentiated from primary tumors, metastatic tumors, and meningiomas at the P < .05 confidence level. Lesions of mixed tumor and treatment-related change had intermediate values. Dynamic MRI can be used to differentiate treatment-related changes from primary tumors in previously treated patient populations based on maximal enhancement rates. Individual case studies demonstrate the clinical significance of these findings.     

Initial experience with Tc-99m-HM-PAO in the study of brain tumors

A preliminary study of the distribution of the 99mTc complex of hexamethylpropylene amine oxime (HM-PAO) in 12 patients with brain neoplasms before, during, and after radiotherapy has been performed. Untreated brain tumors were found to exhibit a range of 99mTc-HM-PAO uptake, varying from areas of markedly increased isotope activity to photopenic areas, when compared to normal brain tissue. A ratio of 99mTc-HM-PAO tumor uptake to contralateral normal tissue uptake was calculated prior to and during radiotherapy. This ratio tended to return towards unity in lesions responding to therapy. A predictable alteration in whole brain 99mTc-HM-PAO uptake during radiotherapy was not demonstrated. Unlike the radiolabeled amines, 99mTc-HM-PAO localizes in primary tumors, probably indicating that its uptake mechanism is independent of non specific amine receptors. 99mTc-HM-PAO may be useful in the study of brain tumor physiology and response to therapy.     

Abnormal baseline brain activity in patients with neuromyelitis optica: A resting-state fMRI study

Purpose

Recent immunopathologic and MRI findings suggest that tissue damage in neuromyelitis optica (NMO) is not limited to spinal cord and optic nerve, but also in brain. Baseline brain activity can reveal the brain functional changes to the tissue damages and give clues to the pathophysiology of NMO, however, it has never been explored by resting-state functional MRI (fMRI). We used regional amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI to investigate how baseline brain activity changes in patients with NMO.

Methods

Resting-state fMRIs collected from seventeen NMO patients and seventeen age- and sex-matched normal controls were compared to investigate the ALFF difference between the two groups. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration were further explored.

Results

Our results showed that NMO patients had significantly decreased ALFF in precuneus, posterior cingulate cortex (PCC) and lingual gyrus; and increased ALFF in middle frontal gyrus, caudate nucleus and thalamus, compared to normal controls. Moderate negative correlations were found between the EDSS and ALFF in the left middle frontal gyrus (r = −0.436, p = 0.040) and the left caudate (r = −0.542, p = 0.012).

Conclusion

The abnormal baseline brain activity shown by resting-state fMRI in NMO is relevant to cognition, visual and motor systems. It implicates a complex baseline brain status of both functional impairments and adaptations caused by tissue damages in these systems, which gives clues to the pathophysiology of NMO.