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Photoacoustic (PA) imaging is capable of probing blood oxygen saturation (sO2), which has been shown to correlate with tissue hypoxia, a promising cancer biomarker. However, wavelength-dependent local fluence changes can compromise sO2 estimation accuracy in tissue. This work investigates using PA imaging with interstitial irradiation and local fluence correction to assess precision and accuracy of sO2 estimation of blood samples through ex vivo bovine prostate tissue ranging from 14% to 100% sO2. Study results for bovine blood samples at distances up to 20 mm from the irradiation source show that local fluence correction improved average sO2 estimation error from 16.8% to 3.2% and maintained an average precision of 2.3% when compared to matched CO-oximeter sO2 measurements. This work demonstrates the potential for future clinical translation of using fluence-corrected and interstitially driven PA imaging to accurately and precisely assess sO2 at depth in tissue with high resolution.

Effects of radioactive 125I particles at different doses on apoptosis of HGC-27 gastric cancer cells were investigated. HGC-27 gastric cancer cell suspension was used to establish a tumor-bearing mouse model. The model was reared for approximately 3 weeks and then divided into the control group (implanted with blank particles), the low dose group (implanted with 1.48×10−7 Bq 125I particles), the medium dose group (implanted with 2.22×10−7 Bq 125I particles) and the high dose group (implanted with 2.96×10−7 Bq 125I particles) (n=15 per group). Six nude mice were randomly sacrificed to collect the tumor tissue and measure tumor volume and mass. TUNEL (TdT-mediated dUTP nick-end labeling) was used for detecting apoptosis of tumor cells, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for detecting the relative expression of Bax, caspase-3 and caspase-8. On the 28th day after implantation, the apoptotic rate in the low, medium and high dose groups was significantly higher than that in the control group, which in the medium and high dose groups was significantly lower than that in the low dose group (P<0.05). On the 28th day after implantation, the relative expression of Bax, caspase-3 and caspase-8 mRNA in the control group was significantly lower than that in the low, medium and high dose groups (P<0.05), which in the low dose group was significantly higher than that in the medium and high dose groups (P<0.05). 125I particles can inhibit the growth of HGC-27 gastric cancer cell transplants and promote the expression of Bax, caspase-3 and caspase-8 mRNA in the tumor tissue. Low-dose 125I particles are significantly more effective than medium- or high-dose 125I particles. [ABSTRACT FROM AUTHOR]

Treatment options for inoperable glioblastoma are limited. Low-dose-rate stereotactic iodine-125 brachytherapy (SBT) has been reported as an effective and low-risk treatment option for circumscribed low-grade gliomas and brain metastases. The present study evaluates this treatment approach for patients with inoperable glioblastoma. Between 1990 and 2012, 201 patients with histologically proven glioblastoma were treated with SBT (iodine-125 seeds; median cumulative surface dose, 60 Gy; median dose-rate, 6 cGy/h; median gross-tumor-volume, 17 ml) either as primary treatment ( n = 103) or at recurrence ( n = 98). In addition to SBT, 90.3 % of patients in the primary treatment group received external boost radiotherapy (median dose, 25.2 Gy). Adjuvant chemotherapy was added for 30.8 % of patients following SBT and consisted of temozolomide for the majority of cases (88.7 %). Procedure-related complications, clinical outcome, progression-free and overall survival (PFS, OS) were evaluated. Median follow-up was 9.8 months. The procedure-related mortality was zero. During follow-up, transient and permanent procedure-related morbidity was observed in 7.5 and 2.0 %, respectively. Calculated from the time of SBT, median OS and PFS rates were 10.5 and 6.2 months, with no significant differences among primary and recurrent tumors (11.1 vs.10.4 months for OS and 6.2 vs. 5.9 months for PFS). For OS, multivariate analysis revealed Karnofsky performance score, age, and adjuvant chemotherapy as independent prognostic factors (all p < 0.01). Low-dose-rate SBT is a relatively safe and potentially effective local treatment option for patients with circumscribed inoperable glioblastoma initially or at recurrence. It deserves prospective validation since it may improve the outcome for a subset of patients with inoperable GBM. [ABSTRACT FROM AUTHOR]

To evaluate the therapeutic efficacy of treating glioblastoma with interstitial irradiation using radioactive seeds. First, the tumor was removed as completely as possible under an operating microscope. Then 125I seeds which had been selected were implanted in the tumor bed followed by routine radiotherapy after the operation. The time of progression (TTP) and overall survival (OS) of the patients were recorded, and statistically compared with patients who had received only surgery and radiotherapy for glioblastoma during the same period. Nineteen patients, who were diagnosed with glioblastoma for the first time, with a mean age of 51.2 years, were involved in this study. Radioactive seeds (8∼20) were implanted into the tumor bed after tumorectomy with a mean surrounding therapeutic dose of 31.6 Gy, followed by an external irradiation dose of 42∼54 Gy. The average TTP in the group with implanted seeds was 42.1±2.4 w (95% confidence interval, 37.2∼46.5 w), and 27.1±2.7 w (95% confidence interval, 24.3∼31.8 w) in the control group. The average OS was 66.3±3.2 w (95% confidence interval, 61.9∼70.4 w) and 47.7±2.6 w (95% confidence interval, 44.4∼50.5 w), respectively. Statistical analysis showed there was a significant difference between two groups. The survival time of patients with glioblastoma can be prolonged through radioactive seed implantation at the time of operation. This therapeutic method can rapidly reduce the tumor volume with a minimum number of seeds to avoid excessive radiation exposure. Because of some shortcomings of this study, such as a small number of patients, and because implantation was performed under the naked eye so that the seed alignment could not be verified accurately, the experience of combining implantation of seeds with external irradiation needs to be investigated further. [ABSTRACT FROM AUTHOR]

Objective To present long-term results after interstitial iodine-125 irradiation of adult patients with de-novo World Health Organization (WHO) Grade II astrocytomas and oligoastrocytomas of the insula of Reil with special respect to the treatment-related risk. Methods 55 consecutively treated patients (from 1979 to 1992) with circumscribed tumors with a diameter <5 cm (astrocytomas: 46 patients, oligoastrocytomas: 9 patients) were included. The reference dose calculated to the outer boundary of the tumor was in the range of 60-100 Gy and the dose rate was low (< 10 cGy/h). Progression-free survival, risk of malignant transformation, survival, and the incidence of radiogenic complications were estimated by the Kaplan-Meier method. Prognostic factors were obtained from the Cox-model. Results Median follow up for the survivors was > 10 years. 5-year (10-year) progression-free survival was 40.7% (20.2%),and 5-year (10-year) survival 54.6 % (28.4%). Malignant transformation occurred in 42.4 % after 5 years. Neither of the Kaplan-Meier curves showed a leveling off over time. Transient (progressive) radiogenic complications were observed in 13 [4] patients (one-year overall complication rate: 18 %), and were significantly associated with a tumor diameter >3.5cm (p<0.001). No long term side-effects were detected and delayed external beam irradiation (in case of tumor progression) did not enhance the risk. Tumor enhancement on CT was the only unfavorable predictor for survival. Conclusion A limited overall prognosis for adult patients with insular WHO grade 11 astrocytomas and oligoastrocytomas was detected. Interstitial 1-125 irradiation offers a minimal-invasive and low-risk treatment option for circumscribed tumors with a diameter <3.5 cm. Larger tumors require further evaluation for optimal treatment. [ABSTRACT FROM AUTHOR]

The safe, effective, clinical application of interstitial laser irradiation to destroy brain tumour tissue requires a knowledge of the relation of the extent of laser-induced (thermal) necrosis to the delivered laser power and total energy, and to time post-irradiation. We have conducted experiments to determine these relationships in normal rabbit brain. Irradiation by a Nd-YAG laser (1064 nm), at powers of 0.5-3.0 W and exposures of 200-1333 s produced well-defined necrotic lesions whose size increased with both the power and the total energy delivered. Lesions of 6 mm diameter made by 0.75 W for 1000s were well tolerated by animals allowed to recover from anaesthesia following irradiation. The diameter of the lesion was greatest at 48 h after irradiation. Following evolution of a characteristic healing response to necrosis in brain, the residual damage at 4 weeks was no greater in volume than that of the acute lesion. The results suggest that low power interstitial Nd-YAG laser photocoagulation in brain can be reliably and safely effected. [ABSTRACT FROM AUTHOR]

The dose-response curve is reported of healthy rat brains exposed interstitially to argon laser light. By means of a 0.4 mm diameter optical fibre, doses of 1 W and 0.25 W were administered, for periods from 0 to 60 s. Well circumscribed oval lesions were obtained, sometimes with unexpected extensions towards a ventricle and even at distances from the main lesion. [ABSTRACT FROM AUTHOR]

In this retrospective review the outcome of 539 patients is evaluated, who from 1979 through 1991 underwent stereotactic biopsy and interstitial irradiation using iodine-125 implants. Permanent (lost) 125-I implants were used in 345 cases (64%) (1979-1985), temporary (removable) implants in 194 cases (36%) (1985-1991). The patients were selected for interstitial irradiation on the basis of histological classification, location and circumscription of their tumours (106 pilocytic astrocytomas, 251 astrocytomas WHO grade II, 29 oligodendrogliomas, 44 oligo-astrocytomas, 75 anaplastic astrocytomas and 34 glioblastomas). Diffusely infiltrative non-delineated gliomas and gliomas crossing the midline were excluded. Five-year survival rates were 77% for pilocytic astrocytomas, 65% for astrocytomas WHO II, 80% for oligo-astrocytomas, and 58% for oligodendrogliomas. The 2-year survival rates were 36% for anaplastic gliomas and 16% for glioblastomas. Operative morbidity due to stereotactic biopsy, implantation, and explantation of seeds was 3.9%. In the subgroups of patients with astrocytomas (WHO-II), pilocytic astrocytomas and malignant gliomas age was a significant factor predicting survival. Patients with astrocytomas WHO II who received temporary implants had a significantly better outcome than those with permanent implants. Radiation toxicity (3.1%) was seen mostly among the permanent (lost) implants. No patients required re-operation due to radionecrosis. The findings among this subgroup of gliomas indicate that interstitial implant irradiation using 125-I is effective in controlling tumour growth and is well tolerated. Patients with differentiated and circumscribed gliomas particularly benefit from the treatment. [ABSTRACT FROM AUTHOR]

We have conducted a phase-I clinical trial of CT guided stereotactic implantation of Ir in the treatment of malignant astrocytomas. During the past year, 16 patients have been implanted with two to four catheters in the residual enhancing portion of their tumor. These patients represent 50% of our total experience with the CT compatible Leksell frame. Each catheter contains three to six high intensity (2.0 to 2.5 mg Ra equivalent) seeds with 0.5 cm separation between the sources. The total activity of Ir per implant has been 30-65 mg radium equivalent. In the 16 patients, 49 catheters have been placed, an average of three targets calculated per patient and no targets have been missed. The radiation exposure to personnel has been surveyed in detail and drops off to less than 2 mr/h six feet from the patient when our custombuilt radiation shield is employed. We have reserved permanent implantation of I for patients with tumors in unusual locations (e.g. pineal) or for individuals with slowly growing non-gliomatous lesions (i.e. meningioma). The tumor volumes have ranged from 12-120 cm. Unique aspects of our implant procedure include the use of a Leksell frame already adapted to the GE-8800 scanner, the use of pre- and post-implant computerized treatment planning programs to determine the dose distribution profiles and the use of adjustable metal collars crimped to the outer catheters to provide ease of insertion, uniform pre-implant catheter length, and protection against source migration. Two of our patients have suffered from subacute radiation reactions, primarily due to delayed cerebral edema and both of these cases have largely resolved. We believe that it is technologically feasible to deliver 5000 rads to the tumor periphery in 50 h without undue patient toxicity or environmental radiation hazard. The system we have been studying is fully compatible with the simultaneous use of mechanical cytoreduction, chemotherapy and interstitial hyperthermia. [ABSTRACT FROM AUTHOR]

A preclinical evaluation of the technical details and dosimetry for temporary high intensityIr brain implants is presented. The canine brain was used for this quality assurance study in which direct in vivo dose measurements were done by thermoluminescent dosimetry (TLD rods). Precise and reproducible positioning of the TLD rods and Ir ribbons were assured by simple accessories which can be utilized in the clinical situation. The neurosurgical procedure for this non-routine interstitial implant of the brain, suitability of type and size of afterloading cannulas and facility for firmly anchoring them to the scalp, and comparison of measured doses with computer-predicted values are details assured by the canine study. Agreement between the in vivo determination and computer-generated doses was consistently in the range 2-5%. Data derived from this preclinical evaluation are currently used in both stereotactic and non-stereotactic brain implants at our institution. Details are presented for the implant procedure, dose measurements and brachytherapy planning for multiple ribbons. The latter incorporates direct interaction on computed tomography (CT) images for a hypothetical patient case. [ABSTRACT FROM AUTHOR]

In this case report a patient with a large intraventricular benign ependymoma is presented. The tumour was treated with stereotactically implanted Iodine-125 seeds and interstitial irradiation. Extension (diameter: 6.5 cm) and volume (112.5 ml) of the lesion caused the application of an unusually low dose (tumour surface dose: 40 Gy). The tumour shrank significantly within a few weeks. Follow-up at nearly 5 years shows the patient to be tumour free. [ABSTRACT FROM AUTHOR]