Patient reported outcomes following MR-guided radiotherapy for prostate cancer: a systematic review and meta-analysis.

PURPOSE: This systematic review provides an overview of literature on the impact of MR-guided radiotherapy (MRgRT) on patient reported outcomes (PROs) in patients with prostate cancer (PC). METHODS: A systematic search was performed in October 2023 in PubMed, EMBASE and Cochrane Library. The PICOS framework (i.e., patient, intervention, comparison, outcome, study design) was used to determine eligibility criteria. Included were studies assessing PROs following MRgRT for PC with sample size >10. Methodological quality was assessed using the ROBINS-I and RoB 2. Relevant mean differences (MD) compared to pre-RT were interpreted using minimal important differences (MID). Meta-analyses were performed using random-effects models. Between-study heterogeneity was assessed using the I2-statistic. RESULTS: Eleven observational studies and one randomized controlled trial (n=897) were included. Nine studies included patients with primary PC with MRgRT as first-line treatment (n=813) and three with MRgRT as second-line treatment (n=84). Substantial risk of bias was found in five studies. EORTC QLQ-C30 and EORTC QLQ-PR25 scores were pooled from three studies, and EPIC-26 scores from four studies. Relevant MDs for the urinary domain were found with the EPIC-26 (MD-10.0 [95%CI -12.0 - -8.1]; I20%) and the EORTC QLQ-PR25 (MD8.6 [95%CI -4.7-22.0]; I297%), both at end-RT to one month follow-up. Relevant MDs for the bowel domain were found with the EPIC-26 (MD-4.7 [95%CI -9.2 - -0.2]; I282%), at end-RT or one month follow-up, but not with the EORTC QLQ-PR25. For both domains, no relevant MDs were found after three months of follow-up. No relevant MDs were found in the general QoL domains of the EORTC QLQ-C30. CONCLUSION: MRgRT for PC results in a temporarily worsening of patient-reported urinary and bowel symptoms during the first month after treatment compared to pre-RT, resolving at 3 months. No clinically relevant changes were found for general QoL domains. These results provide important information for patient counseling and can serve as a benchmark for future studies.

ALLIANCE A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer.

Background: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after neoadjuvant therapy may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. Methods: In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N+) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N+ vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3-4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 (+/- 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 296 evaluable patients (148 per arm) will provide statistical power of 90.5% to detect an 17% increase in cCR rate, at a one-sided alpha=0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse effects. Biospecimens including archival tumor tissue, plasma and buffy coat in EDTA tubes, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and has a current accrual of 312. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Discussion: Building off of data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed the current trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. Trial Registration: Clinicaltrials.gov ID: NCT05610163 ; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

Quality of life and clinical outcomes in rectal cancer patients treated on a 1.5T MR-Linac within the MOMENTUM study.

Background and purpose: This study assessed quality of life (QoL) and clinical outcomes in rectal cancer patients treated with magnetic resonance (MR) guided short-course radiation therapy (SCRT) on a 1.5 Tesla (T) MR-Linac during the first 12 months after treatment. Materials and methods: Rectal cancer patients treated with 25 Gy SCRT in five fractions with curative intent in the Netherlands (2019-2022) were identified in MOMENTUM (NCT04075305). Toxicity (CTCAE v5) and QoL (EORTC QLQ-C30 and -CR29) was primarily analyzed in patients without metastatic disease (M0) and no other therapies after SCRT. Patients who underwent tumor resection were censored from surgery. A generalized linear mixed-model was used to investigate clinically meaningful (≥10) and significant (P < 0.05) QoL changes. Clinical and pathological complete response (cCR and pCR) rates were calculated in patients in whom response was documented. Results: A total of 172 patients were included, of whom 112 patients were primarily analyzed. Acute and late radiation-induced high-grade toxicity were reported in one patient, respectively. CCR was observed in 8/64 patients (13 %), 14/37 patients (38 %) and 13/16 patients (91 %) at three, six and twelve months; pCR was observed in 3/69 (4 %) patients. After 12 months, diarrhea (mean difference [MD] -17.4 [95 % confidence interval [CI] -31.2 to -3.7]), blood and mucus in stool (MD -31.1 [95 % CI -46.4 to -15.8]), and anxiety (MD -22.4 [95 % CI -34.0 to -10.9]) were improved. Conclusion: High-field MR-guided SCRT for the treatment of patients with rectal cancer is associated with improved disease-related symptom management and functioning one year after treatment.

Recommendations for MRI-based contouring of gross tumor volume and organs at risk for radiation therapy of pancreatic cancer.

PURPOSE: Local recurrence is a common and morbid event in patients with unresectable pancreatic adenocarcinoma. A more conformal and targeted radiation dose to the macroscopic tumor in nonmetastatic pancreatic cancer is likely to reduce acute toxicity and improve local control. Optimal soft tissue contrast is required to facilitate delineation of a target and creation of a planning target volume with margin reduction and motion management. Magnetic resonance imaging (MRI) offers considerable advantages in optimizing soft tissue delineation and is an ideal modality for imaging and delineating a gross tumor volume (GTV) within the pancreas, particularly as it relates to conformal radiation planning. Currently, no guidelines have been defined for the delineation of pancreatic tumors for radiation therapy treatment planning. Moreover, abdominal MRI sequences are complex and the anatomy relevant to the radiation oncologist can be challenging. The purpose of this study is to provide recommendations for delineation of GTV and organs at risk (OARs) using MRI and incorporating multiple MRI sequences. METHODS AND MATERIALS: Five patients with pancreatic cancer and 1 healthy subject were imaged with MRI scans either on 1.5T or on 3T magnets in 2 separate institutes. The GTV and OARs were contoured for all patients in a consensus meeting. RESULTS: An overview of MRI-based anatomy of the GTV and OARs is provided. Practical contouring instructions for the GTV and the OARs with the aid of MRI were developed and included in these recommendations. In addition, practical suggestions for implementation of MRI in pancreatic radiation treatment planning are provided. CONCLUSIONS: With this report, we attempt to provide recommendations for MRI-based contouring of pancreatic tumors and OARs. This could lead to better uniformity in defining the GTV and OARs for clinical trials and in radiation therapy treatment planning, with the ultimate goal of improving local control while minimizing morbidity.

Low CHD5 expression activates the DNA damage response and predicts poor outcome in patients undergoing adjuvant therapy for resected pancreatic cancer.

The DNA damage response (DDR) promotes genome integrity and serves as a cancer barrier in precancerous lesions but paradoxically may promote cancer survival. Genes that activate the DDR when dysregulated could function as useful biomarkers for outcome in cancer patients. Using a siRNA screen in human pancreatic cancer cells, we identified the CHD5 tumor suppressor as a gene, which, when silenced, activates the DDR. We evaluated the relationship of CHD5 expression with DDR activation in human pancreatic cancer cells and the association of CHD5 expression in 80 patients with resected pancreatic adenocarcinoma (PAC) by immunohistochemical analysis with clinical outcome. CHD5 depletion and low CHD5 expression in human pancreatic cancer cells lead to increased H2AX-Ser139 and CHK2-Thr68 phosphorylation and accumulation into nuclear foci. On Kaplan-Meier log-rank survival analysis, patients with low CHD5 expression had a median recurrence-free survival (RFS) of 5.3 vs 15.4 months for patients with high CHD5 expression (P=0.03). In 59 patients receiving adjuvant chemotherapy, low CHD5 expression was associated with decreased RFS (4.5 vs 16.3 months; P=0.001) and overall survival (OS) (7.2 vs 21.6 months; P=0.003). On multivariate Cox regression analysis, low CHD5 expression remained associated with worse OS (HR: 3.187 (95% CI: 1.49-6.81); P=0.003) in patients undergoing adjuvant chemotherapy. Thus, low CHD5 expression activates the DDR and predicts for worse OS in patients with resected PAC receiving adjuvant chemotherapy. Our findings support a model in which dysregulated expression of tumor suppressor genes that induce DDR activation can be utilized as biomarkers for poor outcome.

Application of transport phenomena analysis technique to cerebrospinal fluid.

The study of hydrocephalus and the modeling of cerebrospinal fluid flow have proceeded in the past using mathematical analysis that was very capable of prediction phenomenonologically but not well in physiologic parameters. In this paper, the basis of fluid dynamics at the physiologic state is explained using first established equations of transport phenomenon. Then, microscopic and molecular level techniques of modeling are described using porous media theory and chemical kinetic theory and then applied to cerebrospinal fluid (CSF) dynamics. Using techniques of transport analysis allows the field of cerebrospinal fluid dynamics to approach the level of sophistication of urine and blood transport. Concepts such as intracellular and intercellular pathways, compartmentalization, and tortuosity are associated with quantifiable parameters that are relevant to the anatomy and physiology of cerebrospinal fluid transport. The engineering field of transport phenomenon is rich and steeped in architectural, aeronautical, nautical, and more recently biological history. This paper summarizes and reviews the approaches that have been taken in the field of engineering and applies it to CSF flow.

A community-based study of sleep and behaviour problems in 12- to 36-month-old children.

BACKGROUND: While evidence suggests sleep problems are common in young children and linked to behavioural problems, studies of toddlers are rare. This community-based cross-sectional study examined associations between sleep problems and daytime behaviour among 58 children aged 1 to 3 years who attended daycare centres. METHODS: Mothers and daycare providers completed four and three questionnaires, respectively, about children's sleep patterns and behaviour. Two hypotheses were tested: (1) children with higher sleep problem scores would have more behavioural problems by parental and daycare provider report; (2) problematic napping behaviours would be associated with night sleep problems. RESULTS: Mothers' reports of sleep problems were positively associated with children's behavioural problems at home and daycare providers' reports of nap problems were positively correlated with children's behavioural problems at daycare. Daycare providers' reports of children's behavioural problems at daycare were associated with maternal reports of behavioural problems. Older children in the sleep problem group had maternal reports of more behavioural problems. Daycare providers reported that children with sleep problems were less happy at daycare. Children who were happier following naps had less reported night settling difficulties. Children with difficulty settling for naps at daycare had maternal reports of more behavioural problems. CONCLUSIONS: Napping in daycare settings is an important component of toddlers' sleep. Crossover effects between children's sleep and behaviour at daycare and home indicate similarities in mothers' and daycare providers' perceptions. Findings suggest parent and daycare provider interactions include discussions about sleep problems and settling at home and in daycares. Parents and daycare providers would benefit from education about relationships between sleep and behavioural problems.

Convection-enhanced delivery: neurosurgical issues.

Because primary brain tumors treated with surgery, radiation therapy, and chemotherapy have a poor prognosis, this has led investigators to develop new innovative therapies such as targeted toxins. These large molecules do not cross the blood brain barrier and must be delivered into the brain by a technique known as convection-enhanced delivery (CED). When administering these agents, there are a number of pharmacokinetic considerations that must be considered that will directly affect the volume of distribution of the drug being administered and ultimately the therapeutic effect of the agent. A number of different catheter types have been used to perform CED with a hollow fiber design offering several advantages over other variations. Specific parameters have been developed to optimize the placement of the drug delivery catheters in order to enhance drug distribution in the brain. Considerable effort has been expended to identify a reliable way to image the distribution of targeted toxins administered by CED using a combination of magnetic resonance imaging and single photon emission computed tomography. Unfortunately many infusions performed in tumor patients are unsuccessful due to ventricular/subarachnoid leak or pooling of the drug in necrotic tumor tissue. To date, no targeted toxin clinical trial has demonstrated statistically significant clinical results leading to the universal acceptance of this treatment. Other agents such as standard chemotherapy or liposomal preparations have been delivered by CED. Non-neoplastic neurological diseases are being considered for treatment by CED and treating different locations of the brain other that the cerebral hemispheres are under investigation.

Effects of an intervention aimed at reducing night waking and signaling in 6- to 12-month-old infants.

This quasi-experimental one-group pre- and posttest pilot study evaluated an intervention aimed at reducing night waking and signaling for infants between 6 and 12 months of age. Thirty-nine healthy infants and their parents were recruited. Thirty-five infants completed the intervention and data collection. Both parents participated in a group teaching session with telephone follow-up for 2 weeks. Actigraphy and sleep diary data were collected at baseline and 6 and 16 weeks postintervention. We hypothesized a decrease in length and number of infant waking and crying periods and an increase in longest night sleep and nap time. Following the intervention, infants had significantly reduced length of night crying and number of wakes and longer night sleep periods. The intervention warrants evaluation with a randomized controlled design.

Programmable shunt-related suicide attempt.

The treatment of hydrocephalus has benefited recently from the use of programmable shunt valves. These devices can be adjusted using magnets to regulate how much spinal fluid is drained. However, it is unclear to what extent other environmental magnetic sources can affect programmable valves. We present the case of a man who attempted suicide by successfully turning his adjustable valve to a near-maximal setting using a hand-held electromagnet, and discuss other reported cases in order to better understand the effects of environmental magnets on programmable shunt valves.

Measurement and analysis of brain deformation during neurosurgery.

Recent studies have shown that the surface of the brain is deformed by up to 20 mm after the skull is opened during neurosurgery, which could lead to substantial error in commercial image-guided surgery systems. We quantitatively analyze the intraoperative brain deformation of 24 subjects to investigate whether simple rules can describe or predict the deformation. Interventional magnetic resonance images acquired at the start and end of the procedure are registered nonrigidly to obtain deformation values throughout the brain. Deformation patterns are investigated quantitatively with respect to the location and magnitude of deformation, and to the distribution and principal direction of the displacements. We also measure the volume change of the lateral ventricles by manual segmentation. Our study indicates that brain shift occurs predominantly in the hemisphere ipsi-lateral to the craniotomy, and that there is more brain deformation during resection procedures than during biopsy or functional procedures. However, the brain deformation patterns are extremely complex in this group of subjects. This paper quantitatively demonstrates that brain deformation occurs not only at the surface, but also in deeper brain structure, and that the principal direction of displacement does not always correspond with the direction of gravity. Therefore, simple computational algorithms that utilize limited intraoperative information (e.g., brain surface shift) will not always accurately predict brain deformation at the lesion.

Selective cyclooxygenase-2 inhibition does not affect the healing of cutaneous full-thickness incisional wounds in SKH-1 mice.

BACKGROUND: The inducible cyclooxygenase-2 (COX-2) enzyme is upregulated in inflammatory diseases, as well as in epithelial cancers, and has an established role in angiogenesis and tissue repair. OBJECTIVE: Because of these physiological effects and the widespread use of the selective COX-2 inhibitor, celecoxib, we wanted to determine if inhibition of COX-2 would affect incisional skin wound healing. METHODS: Using a cutaneous full-thickness, sutured, incisional wound model in hairless SKH-1 mice, we evaluated the role of COX-2 in the wound healing process by comparing the effects of a nonselective COX inhibitor, diclofenac, with a selective COX-2 inhibitor, SC-791. Healing was monitored for up to 28 days postincision histologically and for recovery of wound strength. RESULTS: COX-2 expression was observed over the first week of healing, peaking at day 3 and was not affected by treatment with the selective COX-2 or nonselective COX inhibitors. Infiltrating macrophages, as well as keratinocytes and dermal fibroblasts at the wound site, expressed COX-2. Neither selective COX-2, nor nonselective COX inhibition had a significant effect on the macroscopic or microscopic morphology of the wounds, whereas dexamethasone treatment resulted in epidermal and granulation tissue atrophy. In addition, neither selective COX-2, nor nonselective COX inhibition altered keratinocyte proliferation and differentiation, dermal angiogenesis or the recovery of wound tensile strength, whereas dexamethasone reduced the tensile strength of the wounds by 30-38% throughout the healing period. CONCLUSIONS: These data indicate that selective COX-2 inhibition does not affect the healing of surgical skin wounds.

Influence of 1.5-Tesla intraoperative MR imaging on surgical decision making.

To determine the frequency that high-field magnetic resonance (MR) imaging sequences influenced surgical decision making during intraoperative MR-guided surgery. From January 1997 to February 2001, 346 MR-guided procedures were performed using a 1.5-Tesla MR system (NT-ACS, Philips Medical Systems). This system can perform functional MR imaging (fMRI), diffusion weighted imaging (DWI), MR spectroscopy (MRS), MR angiography (MRA), and MR venography (MRV) in addition to T1-weighted, T2-weighted, and turbo FLAIR (fluid-attenuated inversion recovery) imaging. FMRI was used to determine areas of brain activation for language, motor function, and memory. DWI was utilized after tumor resection to exclude cerebral ischemia or infarction. MRS was obtained to identify areas of elevated choline that were suspected to correlate with tumor presence. MRA and MRV localized vascular structures adjacent to tumors prior to resection. The intraoperative procedures performed included 140 brain biopsies of which 82 utilized a trajectory guide and prospective stereotaxy. MRS was used in 42 biopsies (30%), of which 29 had turbo spectroscopic imaging (TSI) and 21 had single voxel spectroscopy (SVS). In all biopsy cases, diagnostic tissue was obtained. There were 103 tumor resections of which 18 (17%) had MRS. Functional MRI was used in 17 cases; 3 biopsies (2%) and 14 planned resections (14%). Speech function was localized in 3 cases, memory function in 3, and motor function in 11. In one case where the motor function of the tongue was intimately involved with a low-grade glioma, resection was not attempted. DWI was used in less than 10% of tumor resections. MRA and MRV were performed in 3 (3%) and 2 (2%) of tumor resections, respectively. The imaging capabilities (i.e., fMRI, DWI, MRA, MRV) associated with high-field intraoperative MR influenced surgical decision making primarily for tumor resections. MRS influenced target selection during brain biopsy.

The roles of functional MRI in MR-guided neurosurgery in a combined 1.5 Tesla MR-operating room.

BACKGROUND AND PURPOSE: During MR-guided neurosurgical procedures performed in a combined 1.5 Tesla MR-operating room (MR-OR), we have successfully implemented and validated a functional MRI (fMRI) scheme for efficiently localizing eloquent functional areas and assessing their proximity to a lesion volume immediately prior to the craniotomy. METHODS: The fMRI examination consists of a dynamical blood oxygenation level dependent (BOLD) MR imaging technique and a task paradigm that is designed to activate the brain area of interest. The functional imaging technique was based on gradient-echo (GE) echo-planar imaging (EPI) (TR/TE = 2000-3000/40-50 msec). The motor task paradigm involves a periodic movement task, such as alternating between thumb and the other four fingers as a finger-tapping task, while the language involved a covert repeat of a series of words given as a task stimulus. While patient is performing the task, a dynamical fMRI was performed concurrently covering the volume of interest every 2 or 3 sec. Also, we have used a temporal series averaging (TSA) method for correcting the background drift in the raw fMRI signal, and developed a scheme for presenting fMRI results to neurosurgeons in an intuitive 3-dimensional volume-rendered display format. RESULTS: By using the fMRI scheme, we have successfully performed sixteen fMRI examinations immediately prior to neurosurgery in the combined MR-OR on the same surgical table to localize various eloquent functional areas of interests. TSA was successful in reducing the background drift in the fMRI time course data, and the 3-dimensional volume-rendered display was proven effective in presenting the resulting brain activations to neurosurgeons. More importantly, in three representative cases (one biopsy and two tumor resections) presented, the information provided by fMRI have indeed contributed significantly in making the optimal surgical decisions prior to craniotomy. CONCLUSIONS: Intra-operative fMRI can be an indispensable tool for determining the location of a neighboring eloquent functional area of concern in reference to a targeted lesion. Information provided by fMRI has helped in improving the outcome and clinician confidence of all surgeries performed.

Costs and benefits of intraoperative MR-guided brain tumor resection.

We retrospectively compared the costs and benefits of brain tumor resection in the conventional operating room (cOR) with the interventional magnetic resonance (iMR) suite from 1993-1998. Comparisons were made for adults (diagnosis-related group (DRG) 001) and children (DRG 003) for length of stay (LOS), hospital charges and payments, hospital total direct and indirect costs, readmission rates, repeat resection (RR) interval, and net health outcome. Statistical analysis was with ANOVA, Dunnett's, and Bonferroni tests. For DRG 001, iMR LOS (3.7 days (d)) was 54.9% shorter than for cOR (8.2 d) for first resections (FR) (P < 0.001) and RR (6.0 vs. 8.7 d (31.0%), P < 0.05). IMR hospital charges were 12.2% lower ($4063) for FR and 4.1% lower ($922) for RR than for cOR. Total iMR hospital costs were 14.4% lower ($3415) than for cOR for FR and 3.3% lower ($723) than costs for RR. Cost-to-charge ratio (c/c) for FR was 69.6% (iMR) and 71.4% (cOR) and for RR 70.9% (iMR) and 71.1% (cOR). For DRG 003, iMR LOS (4.5 d) was shorter than for cOR (14.1 d, P < 0.001) for FR and for RR (8.0 vs. 13.3 d). IMR hospital charges were 43.8% lower than for cOR for FR (P < 0.05) and RR. The iMR costs were lower for FR (46.4%, P < 0.01) and RR (44.7%) than cOR. IMR c/c was 71.4% and 74.8% for cOR. For RR, the iMR c/c was 72.8% and 73.9% for cOR. No RR have followed iMR surgery. COR RR rate was 20% in adults and 30% in children. The mean time from iMR surgery was 11.3 months in adults and 18.0 in children. For the cOR, the mean time to RR was 9.3 months in adults and 13.3 in children. This data suggests that iMR surgery improves net health outcomes by reduced LOS, reduced RR, and reduced hospital charges and costs.

Focal intracranial infections due to Propionibacterium acnes: report of three cases.

OBJECTIVE AND IMPORTANCE: Except for its role in shunt infections, Propionibacterium acnes has been of little interest to neurosurgeons. The rarity and indolent nature of focal intracranial infections by P. acnes limit their recognition. Three cases of serious intracranial infection due to this organism are described. CLINCAL PRESENTATION: Three patients with histories of immunosuppression and neurosurgical procedures developed nonspecific, delayed presentations (5 wk to 5 yr after surgery) of intracranial infections. In two patients, radiological investigations showed enhancing lesions that were later found to be brain abscesses. A subdural empyema was found in the third patient. INTERVENTION: All three patients underwent surgical drainage of the purulent collections. P. acnes was isolated in each case, and each patient was treated with a 6-week course of intravenous penicillin. All three patients made good recoveries, and subsequent imaging showed no recurrence of the infectious collections. CONCLUSION: P. acnes is an indolent organism that may rarely cause severe intracranial infections. This organism should be suspected when an intracranial purulent collection is discovered in a patient with a history of neurosurgical procedures. Immunosuppressed patients may be susceptible to this otherwise benign organism. Surgical drainage and treatment with intravenous penicillin should be considered standard therapy.

An efficient chemical shift imaging scheme for magnetic resonance-guided neurosurgery.

An efficient magnetic resonance spectroscopic imaging (MRSI) or chemical shift imaging (CSI) technique based on multiple spin echoes (MSE) has been implemented, validated, and used in both phantom and in vivo MR-guided neurosurgical applications. The key concept of the method is to employ MSE to significantly speed up the data collection rate for mapping hydrogen-containing metabolites. Using an echo train length (ETL) of three per excitation to simultaneously fill three consecutive k-space areas, the total scan time for a spectroscopic image matrix size of 32 x 32 has been shortened to approximately 11 minutes. An interecho spacing time of 273 msec was used to null the phase anomalies of lactate double peaks due to the J-coupling. This allowed a sufficient long data sampling time to achieve 4 Hz spectral resolution. Performing CSI intraopertively during an MR-guided neurosurgical procedure was shown to be feasible at 1.5 T. More importantly, it was shown that more relevant information can be obtained regarding neurochemistry about a targeted lesion, in addition to conventional MR morphological imaging noninvasively. In 25 MR-guided neurosurgical cases, the alleviated choline signal has been found to be consistent with the existence of rapid tumor cell proliferation in the corresponding area. The actual neurobiopsy guided by the spectroscopic imaging method demonstrated that it could provide valuable information in specifying the optimal site in a biopsy procedure, especially in the case involving a nonenhancing tumor. The multiecho scheme has made the CSI technique efficient enough to be routinely used in MR-guided surgical procedures at 1.5 T and also allows the possibility of taking full advantage of MRI capability.

Intra-operative MRI-guided approaches to the pediatric posterior fossa tumors.

INTRODUCTION: The posterior fossa in a child poses a considerable challenge to the neurosurgeon. MRI-guided surgery allows for real time interaction between imaging and the neurosurgeon, not permitted by frameless stereotaxy, and with higher resolution than ultrasound or CT. MATERIALS AND METHODS: The University of Minnesota 1.5 T Phillips interventional MRI was used. From 1997 to 2000, nine posterior fossa intraoperative magnet cases out of eleven were pediatric. The mean age was 6.4 years and the median age 7. Seven midline craniotomies were performed, of which three were re-operations. Two were burr hole placements, one for cyst aspiration and P32 instillation, and the other for tumor biopsy. RESULTS: Two tumors were predominantly in the fourth ventricle, four in the cerebellum, two in the brainstem, and one in the prepontine cystern. Four tumors were juvenile pilocytic astrocytomas, two were anaplastic astrocytomas, and one each was ependymoma, craniopharyngioma cyst, and medulloblastoma. Four patients had complete radiologic resection. Two had maximal resections limited by vital structures. P32 instillation and tumor biopsy were done in a single pass. Follow-up ranged from 3 months to 1.4 years. The cyst that was aspirated and had P32 instillation remains absent. The two mortalities were in the patients with medulloblastoma and anaplastic astrocytoma. There were no intra-operative mortalities. The other patient with anaplastic astrocytoma progressed. The remainder had stable imaging. CONCLUSION: MRI-guided surgery results in improved resection imaging and real-time needle guidance in tumor operations. Its value could lie in low-grade lesions, where maximal resection is most beneficial.

Preliminary assessment of turbo spectroscopic imaging for targeting in brain biopsy.

BACKGROUND AND PURPOSE: Brain biopsy remains an integral and necessary component in the diagnosis of brain lesions. We assessed the ability of turbo spectroscopic imaging (TSI) to provide a physiologically based target for tissue sampling. METHODS: TSI was performed in 26 anesthetized patients immediately before MR-guided brain biopsy. In 10 patients, single-voxel spectroscopy was performed on the TSI-indicated target and correlated with the TSI findings. Biopsy samples were taken from the imaging and spectroscopically defined target(s) under MR guidance, and pathologic findings were compared with preoperative spectra. RESULTS: TSI alone provided a definitive target based on a region of elevated choline in 17 of 21 patients in whom a neoplasm was confirmed. The remaining four neoplasms exhibited relatively low metabolic levels and were difficult to distinguish from the five cases of radiation necrosis seen in this study. TSI findings were in qualitative agreement with those obtained at single-voxel spectroscopy, although TSI spectra exhibited more contamination. Quantitative spectral analysis of TSI data is limited by low spectral resolution. CONCLUSION: TSI is helpful for determining an appropriate biopsy target in heterogeneous lesions. Coupling TSI targeting with conventional imaging and intraoperative confirmation of needle positioning resulted in a 100% diagnostic success rate and increased the clinician's confidence in the histologic findings.

Immunization with dendritic cells pulsed with tumor extract increases survival of mice bearing intracranial gliomas.

The purpose of this study is to investigate the efficacy of dendritic cell-mediated immunotherapy against intracranial gliomas. Cloned DC2.4 dendritic cells originating from C57BL/6 mice were pulsed with glioma GL261 cell extracts and administered i.p. to C57BL/6 mice with intracranial GL261 gliomas. The survival of mice with and without pulsed dendritic cells was monitored after intracranial implantation of the GL261 glioma cells. Fluorescence activated cell sorting (FACS) analysis showed that DC2.4 cells express high levels of MHC class I and class II molecules, costimulatory molecules B7-1 and B7-2, and the cell adhesion molecule ICAM-1. Antigen-presenting capabilities in these dendritic cells were initially characterized in vitro by a mixed lymphocyte reaction, showing that Balb/c CD4+ and CD8+ T cells were able to generate allogeneic responses to DC2.4 cells. Tumor extract-pulsed DC2.4 dendritic cells were then used for the treatment of C57BL/6 mice with syngeneic GL261 gliomas. Animals with intracranial GL261 gliomas and vaccinated i.p. with pulsed DC2.4 dendritic cells exhibited significantly enhanced survival, relative to animals treated with saline or non-pulsed DC2.4 cells alone. In addition, cured animals showed an increased delayed-type hypersensitivity response to GL261 cells and survived when rechallenged with intracranial GL261 gliomas. In summary these results indicate that dendritic cells pulsed with tumor extract can enhance immune responses to tumor antigen and therefore represent a potential immunotherapeutic approach for treating patients with intracranial gliomas.