Roberto Spiegelmann

Early Detection of Response to Radiation Therapy in Patients With Brain Malignancies Using Conventional and High b-Value Diffusion-Weighted Magnetic Resonance Imaging

PURPOSE To study the feasibility of using diffusion-weighted magnetic resonance imaging (DWMRI), which is sensitive to the diffusion of water molecules in tissues, for detection of early tumor response to radiation therapy; and to evaluate the additional information obtained from high DWMRI, which is more sensitive to low-mobility water molecules (such as intracellular or bound water), in increasing the sensitivity to response. PATIENTS AND METHODS Standard MRI and DWMRI were acquired before and at regular intervals after initiating radiation therapy for 10 malignant brain lesions in eight patients. RESULTS One week posttherapy, three of six responding lesions showed an increase in the conventional DWMRI parameters. Another three responding lesions showed no change. Four nonresponding lesions showed a decrease or no change. The early change in the diffusion parameters was enhanced by using high DWMRI. When high DWMRI was used, all responding lesions showed increase in the diffusion parameter and all nonresponding lesions showed no change or decrease. Response was determined by standard MRI 7 weeks posttherapy. The changes in the diffusion parameters measured 1 week after initiating treatment were correlated with later tumor response or no response (P <.006). This correlation was increased to P <.0006 when high DWMRI was used. CONCLUSION The significant correlation between changes in diffusion parameters 1 week after initiating treatment and later tumor response or no response suggests the feasibility of using DWMRI for early, noninvasive prediction of tumor response. The ability to predict response may enable early termination of treatment in nonresponding patients, prevent additional toxicity, and allow for early changes in treatment.

Linear accelerator radiosurgery for vestibular schwannoma

OBJECT The use of radiosurgery in the treatment of acoustic neuromas has increased substantially during the last decade. Most published experience relates to the use of the gamma knife. In this report, the authors review the methods and results of linear accelerator (LINAC) radiosurgery in 44 patients with acoustic neuromas who were treated between 1993 and 1997. METHODS Computerized tomography scanning was selected as the stereotactic imaging modality for target definition. A single, conformally shaped isocenter was used in the treatment of 40 patients; two or three isocenters were used in four patients who harbored very irregular tumors. The radiation dose directed to the tumor border was the only parameter that changed during the study period: in the first 24 patients who were treated the dose was 15 to 20 Gy, whereas in the last 20 patients the dose was reduced to 11 to 14 Gy. After a mean follow-up period of 32 months (range 12-60 months), 98% of the tumors were controlled. The actuarial hearing preservation rate was 71%. New transient facial neuropathy developed in 24% of the patients and persisted to a mild degree in 8%. Radiation dose correlated significantly with the incidence of cranial neuropathy, particularly in large tumors (> or = 4 cm3). CONCLUSIONS Single-isocenter LINAC radiosurgery proved to be an effective treatment for acoustic neuromas in this series, with results that were comparable with those reported for gamma knife radiosurgery and multiple isocenters.

Linear accelerator radiosurgery for meningiomas in and around the cavernous sinus.

OBJECTIVE A retrospective study to evaluate the efficacy and side effects of linear accelerator radiosurgery in the treatment of cavernous sinus meningiomas. METHODS Between 1993 and 2001, 42 patients with meningiomas involving the cavernous sinus underwent linear accelerator radiosurgery at our institution. A mean radiation dose of 14 Gy was delivered to the tumor margin. The median tumor volume was 8.2 cm3 (mean, 8.4 cm3). Median follow-up was 36 months (mean, 38 mo). RESULTS Control of tumor growth was achieved in 97.5% of the patients. There was no mortality or permanent extraocular motor or pituitary dysfunction. Treatment-related complications included new trigeminal neuropathy in 4.7% and a new visual field defect in 2.8%. Two patients required shunt placement after developing hydrocephalus. One patient with symptomatic temporal lobe edema underwent partial excision of the tumor. Improvement of existing cranial neuropathies was noted in 29% of affected trigeminal nerves, in 22% of oculomotor nerves, and in 13% of Cranial Nerves IV and VI. CONCLUSION This study indicates that linear accelerator radiosurgery can achieve a high control rate of meningiomas involving the cavernous sinus with no mortality and a low incidence of morbidity.

Application of transcranial doppler ultrasonography for the diagnosis of brain death.

Objective: To determine the clinical validity of transcranial Doppler ultrasonographic (TCD) signs of total cerebral circulatory arrest for confirmation of brain death and to define the test protocol. Design: Study of a diagnostic test. Setting: General and neurosurgery intensive care units. Patients: 137 patients in a coma (Glasgow Coma Score 3–5), caused by various pathological conditions, observed from January 1992 to July 1998. 84 patients met the clinical criteria of brain death; 43 patients out of 137 received sedative drug therapy and 31 of these developed brain death. Results: Total cerebral circulatory arrest was demonstrated by TCD in 81 patients. All of them proved to be brain dead according to subsequent clinical examination In 29 of 31 patients who had received sedative drug therapy TCD examination showed total cerebral circulatory arrest 12–48 h before the formal confirmation of the diagnosis. In 1 out of 84 clinically brain dead patients a false negative result was obtained. In 2 of 84 cases, no clear signals from intracranial vessels were obtainable. Fifty-three patients who did not meet the clinical criteria for brain death showed no TCD signs of total cerebral circulatory arrest. The specificity of the TCD test for confirmation of brain death was 100 % and the sensitivity 96.5 %. Conclusions: In agreement with previously published data, we conclude that TCD ultrasonography is a highly specific and sensitive confirmatory test and should be included as an additional test in the protocol for the assessment of brain death.

Haemorrhagic complications and the incidence of asymptomatic bleeding associated with stereotactic brain biopsies

SummaryObject. Stereotactic brain biopsy is a routinely used technique for the diagnosis of brain lesions. Due to its minimally invasive nature, the potential risks associated with this procedure are sometimes underestimated. We have retrospectively analyzed the incidence of symptomatic and asymptomatic haemorrhagic complications associated with stereotactic biopsies. Various variables that may contribute to such complications have been retrospectively analyzed.Methods. Medical and radiological records of 355 consecutive patients who underwent a diagnostic stereotactic brain biopsy were reviewed. The incidence of haemorrhage was derived from a routine post-operative CT scan done within 90–120 minutes of the biopsy. Demographic, radiographic, pathological, and clinical data were also extracted and evaluated for their possible association with haemorrhagic complications.Results. Twenty-five patients (7%) experienced haemorrhagic complications associated with stereotactic biopsy, about half of whom (3.4%) were asymptomatic with no impact on the clinical course. Thirteen (3.6%) complications were symptomatic and two patients (0.6%) died. Lesions located in the brainstem were found to have a significantly higher rate of complications compared to other locations. No other variables, such as location, edema, number of biopsy specimens, or pre-existing neurological deficit showed a statistically significant impact on the incidence or severity of haemorrhage. Seven of the symptomatic complications occurred immediately post biopsy, but in six patients they developed within several hours and even days. The overall diagnostic yield of the biopsies was 93.8%, but was somewhat lower in patients experiencing a haemorrhagic complication.Conclusions. Stereotactic brain biopsy was associated with a low incidence of symptomatic haemorrhagic complications, morbidity and mortality, and a high diagnostic yield. About half of the haemorrhagic complications were asymptomatic. Lesions located in the brainstem had a higher rate of complications. No other clinical, radiographic, or pathological variables were found as predictors of increased risk for haemorrhage.

Continuous irrigation-drainage of the subdural space for the treatment of chronic subdural haematoma. A prospective clinical trial

SummaryThirty seven adult patients which chronic subdural haematoma were randomized into two groups. Eighteen patients served as controls and underwent evacuation of the haematoma via burr holes and a gravity dependent closed-system drainage. Nineteen patients comprised the study group. These patients had a continuous irrigation-drainage system installed in an attempt to facilitate the removal of fibrinolytic substances present in the haematoma fluid and to try to reduce the rate of rebleeding from the haematoma membranes. No differences were found between the pre- and post-operative clinical status, haematoma volumes and the degree of CT changes between the two groups. The complication rate was similar in the two groups. One patient in the study group and three patients in the control group required an extended period of drainage (24–48 hours) prior to the removal of the drains. All patients improved following the procedures. Within 30 days post the initial evacuation of the chronic subdural haematoma, re-operation was required in only one patient in the study group as opposed to four of the controls. This difference was not however statistically significant. When the need for re-operation was combined with the need for extended drainage period, a significant difference was shown in favour of the study group. These results indicate that drainage combined with continuous irrigation of the subdural space does not affect the clinical outcome of the patients, but significantly reduces the frequency of inadequate drainage of the haematoma and prevents longer drainage periods and repeated operations.

Stereotactic targeting of the ventrointermediate nucleus of the thalamus by direct visualization with high-field MRI

Objective: To evaluate the ability of high-field MRI to consistently produce high-resolution, anatomical images of the thalamic ventrointermediate nucleus (Vim) suitable for stereotactic targeting. Methods: MR images of the thalamus of patients treated for essential tremor were acquired prior to treatment using a 3-tesla MR system. Similar images were acquired in 6 volunteers using, for comparison, both a 1.5-tesla and a 3.0-tesla system. Results: The thalamic Vim was clearly and consistently delineated on the 3-tesla images. These images were successfully used for target localization in essential tremor patients. In the volunteers data, images acquired using the 1.5-tesla system were inferior to those acquired using the 3-tesla system, lacking the ability to consistently provide reliably defined borders of the Vim. Conclusion: 3-tesla MRI can provide high-quality depiction of the Vim, potentially enabling accurate treatment planning by direct visualization and definition of the targeted Vim.

Hemangioma of the thoracic spine involving multiple adjacent levels: case report.

An unusual case of hemangioma involving three adjacent dorsal vertebrae with a clinical picture of progressive paraparesis is presented.Radiological verification of the lesion can be expected if possible, using plain X-Rays, tomography, CT scan and myelography. The roentgenographic appearances of vertebral hemangioma were characteristic, but only CT revealed the true extent of the disease.Reports of such a case have appeared infrequently in the literature. [Karshner 1936, Bailey 1955, Reeves 1964, Robbins 1958]

Delayed contrast extravasation MRI: a new paradigm in neuro-oncology

BACKGROUND Conventional magnetic resonance imaging (MRI) is unable to differentiate tumor/nontumor enhancing tissues. We have applied delayed-contrast MRI for calculating high resolution treatment response assessment maps (TRAMs) clearly differentiating tumor/nontumor tissues in brain tumor patients. METHODS One hundred and fifty patients with primary/metastatic tumors were recruited and scanned by delayed-contrast MRI and perfusion MRI. Of those, 47 patients underwent resection during their participation in the study. Region of interest/threshold analysis was performed on the TRAMs and on relative cerebral blood volume maps, and correlation with histology was studied. Relative cerebral blood volume was also assessed by the study neuroradiologist. RESULTS Histological validation confirmed that regions of contrast agent clearance in the TRAMs >1 h post contrast injection represent active tumor, while regions of contrast accumulation represent nontumor tissues with 100% sensitivity and 92% positive predictive value to active tumor. Significant correlation was found between tumor burden in the TRAMs and histology in a subgroup of lesions resected en bloc (r(2) = 0.90, P < .0001). Relative cerebral blood volume yielded sensitivity/positive predictive values of 51%/96% and there was no correlation with tumor burden. The feasibility of applying the TRAMs for differentiating progression from treatment effects, depicting tumor within hemorrhages, and detecting residual tumor postsurgery is demonstrated. CONCLUSIONS The TRAMs present a novel model-independent approach providing efficient separation between tumor/nontumor tissues by adding a short MRI scan >1 h post contrast injection. The methodology uses robust acquisition sequences, providing high resolution and easy to interpret maps with minimal sensitivity to susceptibility artifacts. The presented results provide histological validation of the TRAMs and demonstrate their potential contribution to the management of brain tumor patients.

Delayed Contrast Extravasation MRI for Depicting Tumor and Non-Tumoral Tissues in Primary and Metastatic Brain Tumors

The current standard of care for newly diagnosed glioblastoma multiforme (GBM) is resection followed by radiotherapy with concomitant and adjuvant temozolomide. Recent studies suggest that nearly half of the patients with early radiological deterioration post treatment do not suffer from tumor recurrence but from pseudoprogression. Similarly, a significant number of patients with brain metastases suffer from radiation necrosis following radiation treatments. Conventional MRI is currently unable to differentiate tumor progression from treatment-induced effects. The ability to clearly differentiate tumor from non-tumoral tissues is crucial for appropriate patient management. Ten patients with primary brain tumors and 10 patients with brain metastases were scanned by delayed contrast extravasation MRI prior to surgery. Enhancement subtraction maps calculated from high resolution MR images acquired up to 75 min after contrast administration were used for obtaining stereotactic biopsies. Histological assessment was then compared with the pre-surgical calculated maps. In addition, the application of our maps for prediction of progression was studied in a small cohort of 13 newly diagnosed GBM patients undergoing standard chemoradiation and followed up to 19.7 months post therapy. The maps showed two primary enhancement populations: the slow population where contrast clearance from the tissue was slower than contrast accumulation and the fast population where clearance was faster than accumulation. Comparison with histology confirmed the fast population to consist of morphologically active tumor and the slow population to consist of non-tumoral tissues. Our maps demonstrated significant correlation with perfusion-weighted MR data acquired simultaneously, although contradicting examples were shown. Preliminary results suggest that early changes in the fast volumes may serve as a predictor for time to progression. These preliminary results suggest that our high resolution MRI-based delayed enhancement subtraction maps may be applied for clear depiction of tumor and non-tumoral tissues in patients with primary brain tumors and patients with brain metastases.