A Phase 1 Dose-Escalation Study of Oral 5-Aminolevulinic Acid in Adult Patients Undergoing Resection of a Newly Diagnosed or Recurrent High-Grade Glioma.

BACKGROUND: The utility of oral 5-aminolevulinic acid (5-ALA)/protoporphyrin fluorescence for the resection of high-grade gliomas is well documented. This drug has received regulatory approval in Europe but awaits approval in the United States. OBJECTIVE: To identify the appropriate dose and toxicity or harms of 5-ALA used for enhanced intraoperative visualization of malignant brain tumors, reported from a single medical center in the United States. METHODS: Prior to craniotomy for resection of a presumed high-grade glioma, individuals were given oral 5-ALA as part of a rapid dose-escalation scheme. At least 3 patients were selected for each dose level from 10 to 50 mg/kg in 10 mg/kg increments. Adverse events, intensity of tumor fluorescence, and results of biopsies in areas of tumor and the tumor bed under white light and deep blue light were recorded. RESULTS: A total of 19 patients were studied in this phase 1 study. Serious adverse events were unrelated to the ingestion of 5-ALA. At the highest dose level studied (50 mg/kg), 2 out of 6 patients were observed to have transient dermatologic redness and peeling. These were grade 1 adverse events, which were not serious enough to be dose limiting. Patients at higher dose levels (>40 mg/kg) were more likely to have strong tumor fluorescence. There were no instances of false positive fluorescence. CONCLUSION: The use of 5-ALA for brain tumor fluorescence is safe and effective to a dose of 50 mg/kg. Dose-limiting toxicity was not reached in this study.

Image-guided frameless stereotactic needle biopsy in awake patients without the use of rigid head fixation.

OBJECT: Image-guided frameless stereotactic techniques provide an alternative to traditional head-frame fixation in the performance of fine-needle biopsies. However, these techniques still require rigid head fixation, usually in the form of a head holder. The authors report on a series of fine-needle biopsies and brain abscess aspirations in which a frameless technique was used with a patient's head supported on a horseshoe headholder. To validate this technique, they performed an in vitro accuracy study. METHODS: Forty-eight patients underwent fine-needle biopsy of intracranial lesions that ranged in size from 0.9 to more than 107.7 ml; a fiducial-less, frameless, image-guided technique was used without rigid head fixation. In 1 of the 48 patients a cerebral abscess was drained. The accuracy study was performed with a skull phantom that was imaged with a CT scanner and tracked with a registration mask containing light-emitting diodes. The objective was a skin fiducial marker with a 4-mm circular target to accommodate the 2.5-mm biopsy needle. A series of 50 trials was conducted. RESULTS: Diagnostic tissue was obtained on the first attempt in 47 of 48 brain biopsy cases. In 2 cases small hemorrhages at the biopsy site were noted as a complication on the postoperative CT scan. One of these hemorrhages resulted in hand and arm weakness. The accuracy study demonstrated a 98% success rate of the biopsy needle passing through the 4-mm circular target using the registration mask as the registration and tracking device. This demonstrates a ± 0.75-mm tolerance on the targeting method. CONCLUSIONS: The accuracy study demonstrated the ability of the mask to actively track the target and allow navigation to a 4-mm-diameter circular target with a 98% success rate. The frameless, pinless, fiducial-less technique described herein will likely be another safe, fast alternative to frame-based stereotactic techniques for fine-needle biopsy that avoids the potential morbidity of rigid head-pin fixation. Furthermore, it should lend itself to other image-guided applications such as the placement of ventricular catheters for shunting or Ommaya reservoirs.

Stereotactically guided endoscopic port surgery for intraventricular tumor and colloid cyst resection.

BACKGROUND: Intraventricular lesions are challenging entities that may be difficult to resect completely and safely, especially larger lesions with high vascularity or firm consistency. OBJECTIVE: To assess the results of stereotactically guided endoscopic port (SEP) surgery for resection of colloid cysts and intraventricular tumors. METHODS: The authors developed a minimally invasive microsurgical technique for intraventricular surgery using parallel endoscopy to visualize the lesion. Surgical resection was performed via an 11.5-mm transparent conduit (Neuroendoport) deployed under stereotactic guidance. Forty-seven consecutive cases were performed, and all had a minimum 1-year follow-up to assess the efficacy of the technique. RESULTS: For colloid cysts, gross total resection was achieved in 31 (96.9%) of the 32 cases. The transient neurologic morbidity rate was 9.4%; no permanent neurologic morbidity occurred. For intraventricular tumors, gross or near total resection was achieved in 80% of cases. The transient neurological morbidity rate was 6.7%, and no permanent neurological morbidity occurred. CONCLUSION: SEP surgery for colloid cysts and intraventricular tumors proved to be a safe and effective alternative to conventional microsurgical resection. This technique was not limited by the vascularity, friability, or size of any of the lesions.

Optimizing intracranial metastasis detection for stereotactic radiosurgery.

BACKGROUND AND PURPOSE: The authors characterize the detection of additional intracranial metastases in cancer patients at the time of stereotactic radiosurgery (SRS) using a specialized high-resolution magnetic resonance imaging (MRI) protocol. METHODS: A retrospective review of 150 consecutive radiosurgical procedures for patients with < or =5 known metastatic intracranial tumors diagnosed using MRI was undertaken at a single center. On the day of SRS, all patients underwent rigid head fixation in a stereotactic frame followed by a specialized MRI using a 3-dimensional fast spoiled-gradient sequence on a 1.5-tesla magnet with double-dose gadolinium. Axial imaging was performed using 2-mm cuts and no gap. RESULTS: Additional metastases were detected in 29.3% of patients. The number of known tumors before SRS was predictive of additional metastases being found (p = 0.014). In multivariate analysis, we more frequently found additional metastases at radiosurgery in patients with 3-5 previously known metastases (p = 0.005), in patients with non-small cell lung cancer (p = 0.012) and in patients with a longer time interval between their diagnostic MRI and their stereotactic MRI (p = 0.030). Age, sex and prior fractionated radiation therapy were not predictive factors. CONCLUSION: Our specialized protocol of high-resolution, double-dose contrast-enhanced MRI is a reliable method to evaluate the extent of intracranial disease in patients with known brain metastasis. Treatment planning for radiosurgery, radiation therapy and open surgical therapy are all impacted by improved metastasis detection.

Ultrasound registration of the bone surface for surgical navigation.

OBJECTIVE: To allow non-invasive registration of the bone surface for computer-assisted surgery (CAS), this investigation reports the development and evaluation of intraoperative registration using 2D ultrasound (US) images. This approach employs automatic segmentation of the bone surface reflection from US images tagged with the 3D position to enable the application of CAS to minimally invasive procedures. METHODS: The US-based registration method was evaluated in comparison to point-based registration, which is the predominant method in current clinical use. The absolute accuracy of the US-based registration was determined using a phantom pelvis, with fiducial registration providing the ground truth. The relative accuracy was determined by an intraoperative study comparing the US registration to the point-based registration obtained as part of the HipNav experimental protocol. RESULTS: The phantom pelvis study demonstrated equivalent accuracy between point- and US-based registration under in vitro conditions. In the intraoperative study, the US-based registration was sufficiently consistent with the point-based registration to warrant larger-scale clinical trials of this non-invasive registration method. CONCLUSION: Ultrasound-based registration eliminates the need for physical contact with the bone surface as in point-based registration. As a result, non-invasive registration could fully unlock the potential of computer-assisted surgery, enabling development of the next generation of minimally invasive surgical procedures.

Controller for an Axial Flow Blood Pump.

A rotary blood pump inherently provides only one noninvasive "observable'" parameter (motor current) and allows for only one "controllable" parameter (pump speed). To maintain the systemic circulation properly, the pump speed must be controlled to sustain appropriate outlet Hows and perfusion pressure while preventing pulmonary damage caused by extremes in preload. Steady-state data were collected at repeated intervals during chronic trials of the Nimbus AxiPump (Nimbus, Inc., Rancho Cordova, California, U.S.A.) in sheep (n = 7) and calves (n = 12). For each data set, the pump speed was increased at increments of 500 rpm until left ventricular and left atrial emptying was observed by left atrial pressure diminishing to zero. The effect of decreasing preload was evaluated perioperatively by inferior vena cava occlusion at a constant pump speed. Fourier analysis established a relationship between changes in the pump preload and the power spectra of the pump current waveform. Based on these results, a control method was devised to avoid ventricular collapse and maintain the preload within a physiologic range. The objective of this controller is the minimization of the second and third harmonic of the periodic current waveform. This method is intended to provide a noninvasive regulation of the pump by eliminating the need for extraneous transducers.