MRI-assisted radiation therapy planning of brain tumors--clinical experiences in 17 patients

A new and simple method for precise determination of lateral opposed treatment portals was developed and used in 17 patients. Compared to CT, MRI led to significant changes of portals in 59% (10/17) of cases. Individual shielding blocks could be precisely designed by use of our new method. MRI is the procedure of choice in local radiation therapy planning of brain tumors.     

ESTIMATION OF RELATIVE BLOOD VOLUME IN HEAD AND NECK TUMORS

Introduction: The calculation of relative blood volume in head and neck tumor with MR imaging is anew approach that may provide additional hemodynamic information relevant to both untreated and treated tumors. This hemodynamic information is especially usefu l for the differentiation between viable tumor and post surgical changes or rad iation induced scar, and is also beneficial for tumor staging and tumor biopsy.     

What can we learn from the neutron clinical experience for improving ion-beam techniques and high-LET patient selection?

Historically, improvements in radiotherapy have been mainly due to improvements in physical selectivity: beam penetration, collimation, dosimetry, treatment planning; and advances in imaging. Neutrons were the first high-LET (linear energy transfer) radiation to be used clinically and showed improvement in the differential response of radiation resistant tumors and normal tissues. The benefits of fast neutrons (and other forms of high LET radiations) are due to their biological effects: a reduction of the OER, a reduction in the differential cell radiosensitivity related to their position in the mitotic cycle, and a reduction in cellular repair capacity (thus less importance of fractionation). The poor physical selectivity of the early neutron therapy beams introduced a systematic bias in comparison with the photon treatments and created a negative perception for neutron therapy. However, significant improvements in the neutron therapy equipment resulted in a physical selectivity similar to modern MV photon therapy.The tumor types or sites where the best therapeutic results were obtained included inoperable or recurrent salivary gland tumors locally extended prostatic adenocarcinomas, and slowly growing well-differentiated sarcomas. The benefit of neutrons for some other well-defined groups of patients was demonstrated in randomized trials. It was estimated that about 20 % of all radiotherapy patients could benefit from fast neutrons (if neutrons are delivered under satisfactory physical conditions). An important issue for fast neutron therapy is the selection of the types of patients who could most benefit from high-LET radiations. The same issue is raised today with other high-LET radiations (e.g., ¹²C ions). It is reasonable to assume that the same types of patients would benefit from ¹²C irradiation. Of course the better physical selectivity of ion beams enhances the treatment possibilities but this is true for both the high-LET and low-LET radiations (i.e., moving from neutrons to ¹²C ions and from photons to protons, respectively). An important area of research involves developing criteria to identify specific patients suitable for high-LET radiation. One promising technique is to measure the RBE of the cancer cell population in vitro mainly in head and neck tumors. Modern molecular imaging allows the identification of hypoxic or proliferative regions in the tumor. Special MRI examinations are also able to identify hypoxic regions. A promising predictive test recently initiated, is the study of non-repairable double strand breaks but the utility of the technique needs to be confirmed. The extensive experience with fast neutron therapy can greatly assist the transition to high-LET charged-particle therapy.     

An empirical investigation of motion effects in eMRI of interictal epileptiform spikes

We recently developed a functional neuroimaging technique called encephalographic magnetic resonance imaging (eMRI). Our method acquires rapid single-shot gradient-echo echo-planar MRI (repetition time=47 ms); it attempts to measure an MR signal more directly linked to neuronal electromagnetic activity than existing methods. To increase the likelihood of detecting such an MR signal, we recorded concurrent MRI and scalp electroencephalography (EEG) during fast (20-200 ms), localized, high-amplitude (>50 μV on EEG) cortical discharges in a cohort of focal epilepsy patients. Seen on EEG as interictal spikes, these discharges occur in between seizures and induced easily detectable MR magnitude and phase changes concurrent with the spikes with a lag of milliseconds to tens of milliseconds. Due to the time scale of the responses, localized changes in blood flow or hemoglobin oxygenation are unlikely to cause the MR signal changes that we observed. While the precise underlying mechanisms are unclear, in this study, we empirically investigate one potentially important confounding variable — motion. Head motion in the scanner affects both EEG and MR recording. It can produce brief “spike-like” artifacts on EEG and induce large MR signal changes similar to our interictal spike-related signal changes. In order to explore the possibility that interictal spikes were associated with head motions (although such an association had never been reported), we had previously tracked head position in epilepsy patients during interictal spikes and explicitly demonstrated a lack of associated head motion. However, that study was performed outside the MR scanner, and the root-mean-square error in the head position measurement was 0.7 mm. The large inaccuracy in this measurement therefore did not definitively rule out motion as a possible signal generator. In this study, we instructed healthy subjects to make deliberate brief (<500 ms) head motions inside the MR scanner and imaged these head motions with concurrent EEG and MRI. We compared these artifactual MR and EEG data to genuine interictal spikes. While per-voxel MR and per-electrode EEG time courses for the motion case can mimic the corresponding time courses associated with a genuine interictal spike, head motion can be unambiguously differentiated from interictal spikes via scalp EEG potential maps. Motion induces widespread changes in scalp potential, whereas interictal spikes are localized and have a regional fall-off in amplitude. These findings make bulk head motion an unlikely generator of the large spike-related MR signal changes that we had observed. Further work is required to precisely identify the underlying mechanisms.     

Quantitative combination of volumetric MR imaging and MR spectroscopy data for the discrimination of meningiomas from metastatic brain tumors by means of pattern recognition

The analysis of information derived from magnetic resonance imaging (MRI) and spectroscopy (MRS) has been identified as an important indicator for discriminating among different brain pathologies. The purpose of this study was to investigate the efficiency of the combination of textural MRI features and MRS metabolite ratios by means of a pattern recognition system in the task of discriminating between meningiomas and metastatic brain tumors. The data set consisted of 40 brain MR image series and their corresponding spectral data obtained from patients with verified tumors. The pattern recognition system was designed employing the support vector machines classifier with radial basis function kernel; the system was evaluated using an external cross validation process to render results indicative of the generalization performance to “unknown” cases. The combination of MR textural and spectroscopic features resulted in 92.15% overall accuracy in discriminating meningiomas from metastatic brain tumors. The fusion of the information derived from MRI and MRS data might be helpful in providing clinicians a useful second opinion tool for accurate characterization of brain tumors.     

Tissue characterization of brain tumors during and after pion radiation therapy

Negative Pi-mesons (pions) are applied at the Paul Scherrer Institute in the radiotherapy of highly malignant gliomas using a dose escalation program. The therapy effects of 7 randomly selected patients were followed up by 62 MRI examinations. The quantification of the effects is based on the relaxation times T1 and T2, which are acquired by a new designed multi-echo multiple saturation recovery imaging technique. As a summary of the results, roughly two reaction types are observed. For both types the relaxation times increase up to two to three months after the radiation therapy. Then in one type (two patients) the T1 and T2 values of the tumors, and of the edemas surrounding the tumors, further increase, indicating an unfavorable prognosis. In the other type (five patients) the relaxation times drop down towards, or even below, their initial values, reflecting the onset of the reparation processes in the tissue. This later behaviour reflects an at least temporary control of the disease; that is, the short term prognosis for these patients is more favorable. It further can be concluded, with respect to our MR parameters, that the radiotolerance of healthy brain tissue is much higher than that of malignant glioma tissue, despite the fact that these tumors are very seldom definitively radiosensible.     

Bilateral neurostimulation systems used for deep brain stimulation: in vitro study of MRI-related heating at 1.5 T and implications for clinical imaging of the brain

Deep brain stimulation (DBS) is used increasingly in the field of movement disorders. The implanted electrodes create not only a prior risk to patient safety during MRI, but also a unique opportunity in the collection of functional MRI data conditioned by direct neural stimulation. We evaluated MRI-related heating for bilateral neurostimulation systems used for DBS with an emphasis on assessing clinically relevant imaging parameters. Magnetic resonance imaging was performed using transmit body radiofrequency (RF) coil and receive-only head RF coil at various specific absorption rates (SARs) of RF power. In vitro testing was performed using a gel-filled phantom with temperatures recorded at the electrode tips. Each DBS electrode was positioned with a single extension loop around each pulse generator and a single loop at the "head" end of the phantom. Various pulse sequences were used for MRI including fast spin-echo, echo-planar imaging, magnetization transfer contrast and gradient-echo techniques. The MRI sequences had calculated whole-body averaged SARs and local head SARs ranging from 0.1 to 1.6 W/kg and 0.1 to 3.2 W/kg, respectively. Temperature elevations of less than 1.0 degrees C were found with the fast spin-echo, magnetization transfer contrast, gradient-echo and echo-planar clinical imaging sequences. Using the highest SAR levels, whole-body averaged, 1.6 W/kg, local exposed-body, 3.2 W/kg, and local head, 2.9 W/kg, the temperature increase was 2.1 degrees C. These results showed that temperature elevations associated with clinical sequences were within an acceptable physiologically safe range for the MR conditions used in this evaluation, especially for the use of relatively low SAR levels. Notably, these findings are highly specific to the neurostimulation systems, device positioning technique, MR system and imaging conditions used in this investigation.     

A microstrip transmission line volume coil for human head MR imaging at 4T

A high-frequency RF volume coil based on the use of microstrip transmission line (MTL) has been developed for in vivo 1H MR applications on the human head at 4T. This coil is characterized by major advantages: (i) completely distributed coil circuit, (ii) high-quality factor (Q), (iii) simple coil structure, and (iv) better sensitivity and less signal-intensity variation in the MR image of the human head compared with an RF shielded birdcage coil of similar coil size. The proposed MTL volume coil does not require additional RF shielding for preventing Q degradation from radiation losses due to the unique MTL structure; thus, it provides a maximal useable space inside the volume coil when compared with most volume coils available at high fields with the same overall coil size. The intrinsic B(1) distribution of the MTL volume coil effectively compensates for the dielectric resonance effect at 4T and improves the signal homogeneity in human head MR images in the transaxial planes. The results of this study demonstrate that the MTL volume coil design provides an efficient and simple solution to RF volume coil design for human MR studies at high fields.     

Rapid passive MR catheter visualization for endovascular therapy using nonsymmetric truncated k-space sampling strategies

Passive catheter tracking guidance by MRI is a promising approach for endovascular therapy that may have several clinical advantages over the more frequently employed active MR approaches. However, real-time MR passive tracking is problematic because it is difficult to have an image update rate >1 Hz and preserve adequate spatial and image contrast resolution. One solution for improving real-time temporal performance is the use of nonsymmetric truncated k-space sampling strategies, which acquire only a fraction of the data in both the readout and phase-encoding directions. This article investigated these acquisition strategies in combination with using (a) multicycle projection dephaser (mcPD) gradients for background suppression and (b) the projection-onto-convex sets (POCS) algorithm to reconstruct the images. The use of mcPD gradients allowed the data sampling strategies to exploit the k-space energy structure of the catheter, and POCS allowed reconstruction of high-quality MR images that were suitable for real-time passive catheter tracking and demonstrated improved geometric representations of catheter width and tip position compared to zero filling. The use of nonsymmetric truncated k-space reduced the total acquisition time.     

MR imaging of excessively obese patients: the use of an open permanent magnet

Excessive obesity can pose a limitation to both clinical and radiographic evaluation. Although CT and MR have revolutionized head and body imaging, patients with weights above 300 lb present a restriction of these imaging modalities. Magnetic resonance imaging (MRI) is well suited for imaging excessively obese patients, because the RF used does not have difficulty in penetrating large amounts of adipose tissue as ionizing radiation or sound waves does. The limitations of conventional MR imaging in these obese patients are the gantry size and the table weight limit. The recent development of a new low field MR imager with a larger gantry size and greater weight capacity, has the potential for imaging obese patients that cannot be evaluated by standard CT or MR. In this paper, we report our experience in imaging nine excessively obese patients with weights between 350 and 490 lb using a permanent magnet operating at 0.064 T.     

The use of T2 distribution to study tumor extent and heterogeneity in head and neck cancer

Demarcation of the extent of malignant tissue is essential for planning a course of radiotherapy. MR images may provide additional information for delineating the target volume because of the large difference in the proton magnetic resonance relaxation times between normal and malignant tissues. In 13 patients with head and neck tumors the distribution of the proton spin-spin relaxation times, T2, at 1.5 Tesla were evaluated throughout the physician designated target volume and normal surrounding tissue. The T2 values within the tumor were always elevated compared with normal tissue, the highest values being in the nominal center of the tumor and decreasing toward the periphery. The regional distribution of T2 values within the tumor is a measure of the tissue heterogeneity within the tumor volume. In addition, the large differences in T2 relaxation times between normal and disease tissues were used in a computer algorithm to automatically demarcate the boundary of abnormal tissue in each axial MRI section. This potentially could significantly expedite the time required to identify the target volume on multiple sections and thus remove one of the major time constraints for 3D treatment planning.     

Hepatic vessel segmentation using variational level set combined with non-local robust statistics

Hepatic vessel segmentation is a challenging step in therapy guided by magnetic resonance imaging (MRI). This paper presents an improved variational level set method, which uses non-local robust statistics to suppress the influence of noise in MR images. The non-local robust statistics, which represent vascular features, are learned adaptively from seeds provided by users. K-means clustering in neighborhoods of seeds is utilized to exclude inappropriate seeds, which are obviously corrupted by noise. The neighborhoods of appropriate seeds are placed in an array to calculate the non-local robust statistics, and the variational level set formulation can be constructed. Bias correction is utilized in the level set formulation to reduce the influence of intensity inhomogeneity of MRI. Experiments were conducted over real MR images, and showed that the proposed method performed better on small hepatic vessel segmentation compared with other segmentation methods.     

Gliomatosis cerebri: clinical, neurochemical and neuroradiological response to temozolomide administration

Gliomatosis cerebri is a rare form of diffusely infiltrating glioma that is typically resistant to conventional chemotherapy and radiation therapy and carries a poor prognosis. Temozolomide has shown antineoplastic activity against malignant gliomas and more recently was beneficial in one patient with gliomatosis cerebri. To make an objective assessment of the effect of long-term temozolomide administration in a patient with gliomatosis cerebri we used brain proton magnetic resonance spectroscopy and structural MRI. A 46-year-old man with gliomatosis cerebri was treated with temozolomide (200 mg/m(2) per day for 5 days every 28 days). Twenty cycles of temozolomide resulted in a marked reduction in choline and scyllo-inositol content, as detected using brain proton MR spectroscopy, indicating reduced tumor cellularity and/or growth rate. Neurochemical improvements were associated with normalization of the signal intensity in most of the previously affected cerebral regions and regression of mass effect on MRI. A left pyramidal syndrome, present at the start of the treatment, disappeared. Our observation lends support to larger clinical trials evaluating the use of temozolomide to treat this brain tumor.     

Repeatability of arterial input functions and kinetic parameters in muscle obtained by dynamic contrast enhanced MR imaging of the head and neck

BackgroundQuantification of pharmacokinetic parameters in dynamic contrast enhanced (DCE) MRI is heavily dependent on the arterial input function (AIF). In the present patient study on advanced stage head and neck squamous cell carcinoma (HNSCC) we have acquired DCE-MR images before and during chemo radiotherapy. We determined the repeatability of image-derived AIFs and of the obtained kinetic parameters in muscle and compared the repeatability of muscle kinetic parameters obtained with image-derived AIF's versus a population-based AIF.Materials and methodsWe compared image-derived AIFs obtained from the internal carotid, external carotid and vertebral arteries. Pharmacokinetic parameters (v_e, K^trans, k_ep) in muscle—located outside the radiation area—were obtained using the Tofts model with the image-derived AIFs and a population averaged AIF. Parameter values and repeatability were compared. Repeatability was calculated with the pre- and post-treatment data with the assumption of no DCE-MRI measurable biological changes between the scans.ResultsSeveral parameters describing magnitude and shape of the image-derived AIFs from the different arteries in the head and neck were significantly different. Use of image-derived AIFs led to higher pharmacokinetic parameters compared to use of a population averaged AIF. Median muscle pharmacokinetic parameters values obtained with AIFs in external carotids, internal carotids, vertebral arteries and with a population averaged AIF were respectively: v_e (0.65, 0.74, 0.58, 0.32), K^trans (0.30, 0.21, 0.13, 0.06), k_ep (0.41, 0.32, 0.24, 0.18). Repeatability of pharmacokinetic parameters was highest when a population averaged AIF was used; however, this repeatability was not significantly different from image-derived AIFs.ConclusionImage-derived AIFs in the neck region showed significant variations in the AIFs obtained from different arteries, and did not improve repeatability of the resulting pharmacokinetic parameters compared with the use of a population averaged AIF. Therefore, use of a population averaged AIF seems to be preferable for pharmacokinetic analysis using DCE-MRI in the head and neck area.     

Assessment of absolute blood volume in carcinoma by USPIO contrast-enhanced MRI

OBJECTIVES: The characterization of tumor vasculature is essential in studying tumor physiology. The aim of this study was to develop a new method - based on water proton MR density measurements, in combination with ultrasmall superparamagnetic iron oxide (USPIO) administration - to measure absolute blood volume (BV) in murine colon carcinoma. MATERIALS AND METHODS: MRI experiments were performed at 7 T. CPMG imaging was performed on subcutaneous murine colon carcinoma in six mice before and after administration of an USPIO blood-pool contrast agent. Density maps were obtained from the signal amplitude at TE=0 of the CPMG decay fit. Post-USPIO density maps were subtracted from pre-USPIO density maps to quantitatively yield absolute tumor BV maps. In a separate group of mice (n=6), the relative vascular area (RVA) of tumors was determined by immunohistochemistry. RESULTS: Ultrasmall superparamagnetic iron oxide administration resulted in a small decrease in the water proton MR density. The BV averaged over the six tumors was 4.6+/-1.6%. The value of the RVA measured by immunohistochemical staining was equal to 3.9+/-2.2%. CONCLUSIONS: After administration of an USPIO blood-pool agent (T(2) relaxivity > 100 mM(-1) s(-1)), the blood water protons become MRI invisible, and pixel-by-pixel BV map can be obtained by subtracting the calculated post-USPIO density map from the pre-USPIO density map. The value of absolute BV obtained with this novel MR approach is in good agreement with the value of the relative vascular measured by immunohistochemical staining.     

Magnetic resonance imaging of bone after radiation

Magnetic resonance imaging (MRI) was performed in 22 patients at various times (0-3) years) following radiation therapy to the spine. T1 and T2 weighted images were obtained at 0.5 Tesla. Increased signal was seen after 800-6000 rads (8-60 Gy). Marrow effects corresponded to radiation ports. Recurrent tumor was clearly separated from fatty replacement. This was much better seen on T1 weighted images. Five patients that had MRI during their course of radiotherapy (XRT) did not have increased signal on T1 images of the bone marrow. The earliest fatty marrow change was seen nine days following completion of 3000 rads (30 Gy) XRT over one month's duration. One patient who received 800 rads (8 Gy) to the upper thoracic spine for eosinophilic granuloma had no radiation effects on MRI when imaged 16 days following completion of XRT given over five days. Fatty marrow change was seen in this patient on MRI six months later. MRI was particularly useful in defining the extent of prior radiation effects when repeat therapy was needed.     

Enhancing the discrimination accuracy between metastases, gliomas and meningiomas on brain MRI by volumetric textural features and ensemble pattern recognition methods

Three-dimensional (3D) texture analysis of volumetric brain magnetic resonance (MR) images has been identified as an important indicator for discriminating among different brain pathologies. The purpose of this study was to evaluate the efficiency of 3D textural features using a pattern recognition system in the task of discriminating benign, malignant and metastatic brain tissues on T1 postcontrast MR imaging (MRI) series. The dataset consisted of 67 brain MRI series obtained from patients with verified and untreated intracranial tumors. The pattern recognition system was designed as an ensemble classification scheme employing a support vector machine classifier, specially modified in order to integrate the least squares features transformation logic in its kernel function. The latter, in conjunction with using 3D textural features, enabled boosting up the performance of the system in discriminating metastatic, malignant and benign brain tumors with 77.14%, 89.19% and 93.33% accuracy, respectively. The method was evaluated using an external cross-validation process; thus, results might be considered indicative of the generalization performance of the system to "unseen" cases. The proposed system might be used as an assisting tool for brain tumor characterization on volumetric MRI series.     

Low field thoracic MRI--a fast and radiation free routine imaging modality in children

Radiography of the chest is the most frequently performed radiological examination in pediatric imaging. However, it is associated with the application of ionizing radiation. In order to avoid ionizing radiation in children a new and very fast MRI technique has been developed at our center as an alternative to the pediatric chest X-ray. 100 patients who had received a chest X-ray were additionally investigated in a 0.2 T low-field MR-scanner by a modified true FISP sequence with an acquisition time of 3.6-4.6 s for a coronal triple-slice scan. X-ray and MR images were independently evaluated and later compared by two pediatric radiologists. Total investigation times (door-to-door time) for X-ray and MRI were comparable. The signal-to-noise ratio for lung parenchyma was 4.6-7.3. Of 189 pathologic findings 165 were depicted on MR images as well as radiographs, 18 were noted on MRIs only, 6 on X-rays only. Overall kappa was 0.87. True FISP MRI may be a good alternative to conventional chest X-ray. The main advantages are: fast imaging free of ionizing radiation, easy performance, no need for special equipment, optional imaging in all 3 planes, good image quality, and a high diagnostic value.     

Laryngeal Chondroma

Cartilaginous tumors of the larynx represent less than 1% of laryngeal tumors. Chondroma and "low-grade" chondrosarcoma are the most common; 70%-75% of these tumors arise on the endolaryngeal surface of the posterior lamina of the cricoid cartilage. The clinical presentation is varied and directly dependent on the size and location of the tumor; stridor, hoarseness, dyspnea, or a neck mass are common presenting signs. CT scanning in the axial plane is the mainstay of radiographic imaging due to its ability to show size, extent of the tumor, and invasion into surrounding structures. Surgical extirpation is the standard therapy with no role for radiation therapy or chemotherapy. Although significant recurrence rates have been reported, there is not a significant difference between initial conservative therapy followed by salvage therapy versus initial radical therapy.     

Magnetic resonance imaging of malignant fibrous histiocytoma

The magnetic resonance imaging (MRI) changes in 39 patients with malignant fibrous histiocytoma (MFH) were reviewed retrospectively. Twenty-one sarcomas were in the lower extremity, five each in the upper extremity and trunk, two each in the neck and heart, and one each in the maxillary sinus, sella turcica, tongue, and spermatic cord. The examinations were performed with spin-echo sequences on a 1.5 Tesla Signa Scanner (GE, Milwaukee WI). Twenty-two tumors exhibited intermediate signal intensity on T1-weighted images and 23 were of high signal intensity on T2-weighted images. There was no significant differences in signal intensity of 12 preoperative and 13 recurrent neoplasms. Twelve of 13 patients were correctly diagnosed as having postoperative changes. The MR sensitivity and specificity for detecting a neoplasm were 96% and 83% respectively, but the signal changes were nonspecific for MFH. When compared to CT in 14 patients, MR better defined the extent of the MFH, its relationship to surrounding tissues and vessels, and best differentiated residual or recurrent disease from postoperative changes when examined at least 3 months after surgery.