A few years later, researchers perf

A few years later, researchers performed a first-in-humantrial of noninvasive MRgFUS BBB opening in patients withmalignant glioma, using concurrent systemic administrationof temozolomide chemotherapy (Table 1) (92). T1-weightedMR images demonstrated a 15% to 50% increase in signalenhancement, indicating transient BBB opening in thetarget tissue (Figure 11). Approximately 24 h after FUS andchemotherapeutic administration, the patients underwentcraniotomy and tumor resection. Sonicated and unsonicatedperitumor tissue samples were collected and the tissuechemotherapy concentrations were measured. Note thatduring the trial, the chemotherapy agent was switched from liposomal doxorubicin to temozolomide, and limited resectabletumor volume in three of five patients prevented statisticalanalysis of the tumor samples. Nevertheless, the researchersobserved a chemotherapy concentration that was 7.7 timeshigher in the sonicated peritumor tissue than in the unsonicatedperitumor tissue in one patient.Another group of researchers subsequently tried to enhancethe treatment effect by creating multiple BBB openings withMRgFUS (Table 1) (93). In this study, 6 patients who underwenta gross total resection of malignant glioma received 6 cycles oftemozolomide with associated FUS BBB opening performed atthe beginning of each 4-week cycle. Patients underwent followup MRI 1 year after the first chemotherapy cycle (6 months afterthe last chemotherapy cycle), and there was no evidence of anyFUS-related adverse effects.