Functional Imaging of Malignant Gliomas with CT Perfusion

The overall survival of patients with malignant gliomas remains dismal despite multimodality treatments. Computed tomography (CT) perfusion is a functional imaging tool for assessing tumour hemodynamics. The goals of this thesis are to 1) improve measurements of various CT perfusion parameters and 2) assess treatment outcomes in a rat glioma model and in patients with malignant gliomas. Chapter 2 addressed the effect of scan duration on the measurements of blood flow (BF), blood volume (BV), and permeability-surface area product (PS). Measurement errors of these parameters increased with shorter scan duration. A minimum scan duration of 90 s is recommended. Chapter 3 evaluated the improvement in the measurements of these parameters by filtering the CT perfusion images with principal component analysis (PCA). From computer simulation, measurement errors of BF, BV, and PS were found to be reduced. Experiments showed that CT perfusion image contrast-to-noise ratio was improved. Chapter 4 investigated the efficacy of CT perfusion as an early imaging biomarker of response to stereotactic radiosurgery (SRS). Using the C6 glioma model, we showed that responders to SRS (surviving \u3e 15 days) had lower relative BV and PS on day 7 post-SRS when compared to controls and non-responders (P \u3c 0.05). Relative BV and PS on day 7 post-SRS were predictive of survival with 92% accuracy. Chapter 5 examined the use of multiparametric imaging with CT perfusion and 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) to identify tumour sites that are likely to correlate with the eventual location of tumour progression. We developed a method to generate probability maps of tumour progression based on these imaging data. Chapter 6 investigated serial changes in tumour volumetric and CT perfusion parameters and their predictive ability in stratifying patients by overall survival. Pre-surgery BF in the non-enhancing lesion and BV in the contrast-enhancing lesion three months after radiotherapy had the highest combination of sensitivities and specificities of ≥ 80% in predicting 24 months overall survival. iv Optimization and standardization of CT perfusion scans were proposed. This thesis also provided corroborating evidence to support the use of CT perfusion as a biomarker of outcomes in patients with malignant gliomas

Dynamic perfusion CT in brain tumors.

Dynamic perfusion CT (PCT) is an imaging technique for assessing the vascular supply and hemodynamics of brain tumors by measuring blood flow, blood volume, and permeability-surface area product. These PCT parameters provide information complementary to histopathologic assessments and have been used for grading brain tumors, distinguishing high-grade gliomas from other brain lesions, differentiating true progression from post-treatment effects, and predicting prognosis after treatments. In this review, the basic principles of PCT are described, and applications of PCT of brain tumors are discussed. The advantages and current challenges, along with possible solutions, of PCT are presented

CT Perfusion Imaging as an Early Biomarker of Differential Response to Stereotactic Radiosurgery in C6 Rat Gliomas

BACKGROUND: The therapeutic efficacy of stereotactic radiosurgery for glioblastoma is not well understood, and there needs to be an effective biomarker to identify patients who might benefit from this treatment. This study investigated the efficacy of computed tomography (CT) perfusion imaging as an early imaging biomarker of response to stereotactic radiosurgery in a malignant rat glioma model. METHODS: Rats with orthotopic C6 glioma tumors received either mock irradiation (controls, N = 8) or stereotactic radiosurgery (N = 25, 12 Gy in one fraction) delivered by Helical Tomotherapy. Twelve irradiated animals were sacrificed four days after stereotactic radiosurgery to assess acute CT perfusion and histological changes, and 13 irradiated animals were used to study survival. Irradiated animals with survival \u3e15 days were designated as responders while those with survival ≤15 days were non-responders. Longitudinal CT perfusion imaging was performed at baseline and regularly for eight weeks post-baseline. RESULTS: Early signs of radiation-induced injury were observed on histology. There was an overall survival benefit following stereotactic radiosurgery when compared to the controls (log-rank P CONCLUSIONS: Response to stereotactic radiosurgery was heterogeneous, and early selection of responders and non-responders was possible using CT perfusion imaging. Validation of CT perfusion indices for response assessment is necessary before clinical implementation

Survival prediction in high-grade gliomas using CT perfusion imaging.

Patients with high-grade gliomas usually have heterogeneous response to surgery and chemoirradiation. The objectives of this study were (1) to evaluate serial changes in tumor volume and perfusion imaging parameters and (2) to determine the value of these data in predicting overall survival (OS). Twenty-nine patients with World Health Organization grades III and IV gliomas underwent magnetic resonance (MR) and computed tomography (CT) perfusion examinations before surgery, and 1, 3, 6, 9, and 12 months after radiotherapy. Serial measurements of tumor volumes and perfusion parameters were evaluated by receiver operating characteristic analysis, Cox proportional hazards regression, and Kaplan-Meier survival analysis to determine their values in predicting OS. Higher trends in blood flow (BF), blood volume (BV), and permeability-surface area product in the contrast-enhancing lesions (CEL) and the non-enhancing lesions (NEL) were found in patients with OS \u3c 18 months compared to those with OS ≥ 18 months, and these values were significant at selected time points (P \u3c 0.05). Only CT perfusion parameters yielded sensitivities and specificities of ≥70 % in predicting 18 and 24 months OS. Pre-surgery BF in the NEL and BV in the CEL and NEL 3 months after radiotherapy had sensitivities and specificities \u3e80 % in predicting 24 months OS in patients with grade IV gliomas. Our study indicated that CT perfusion parameters were predictive of survival and could be useful in assessing early response and in selecting adjuvant treatment to prolong survival if verified in a larger cohort of patients

Improving quantitative CT perfusion parameter measurements using principal component analysis.

RATIONALE AND OBJECTIVES: To evaluate the improvements in measurements of blood flow (BF), blood volume (BV), and permeability-surface area product (PS) after principal component analysis (PCA) filtering of computed tomography (CT) perfusion images. To evaluate the improvement in CT perfusion image quality with poor contrast-to-noise ratio (CNR) in vivo. MATERIALS AND METHODS: A digital phantom with CT perfusion images reflecting known values of BF, BV, and PS was created and was filtered using PCA. Intraclass correlation coefficients and Bland-Altman analysis were used to assess reliability of measurements and reduction in measurement errors, respectively. Rats with C6 gliomas were imaged using CT perfusion, and the raw CT perfusion images were filtered using PCA. Differences in CNR, BF, BV, and PS before and after PCA filtering were assessed using repeated measures analysis of variance. RESULTS: From simulation, mean errors decreased from 12.8 (95% confidence interval [CI] = -19.5 to 45.0) to 1.4 mL/min/100 g (CI = -27.6 to 30.4), 0.2 (CI = -1.1 to 1.4) to -0.1 mL/100 g (CI = -1.1 to 0.8), and 2.9 (CI = -2.4 to 8.1) to 0.2 mL/min/100 g (CI = -3.5 to 3.9) for BF, BV, and PS, respectively. Map noise in BF, BV, and PS were decreased from 51.0 (CI = -3.5 to 105.5) to 11.6 mL/min/100 g (CI = -7.9 to 31.2), 2.0 (CI = 0.7 to 3.3) to 0.5 mL/100 g (CI = 0.1 to 1.0), and 8.3 (CI = -0.8 to 17.5) to 1.4 mL/min/100 g (CI = -0.4 to 3.1), respectively. For experiments, CNR significantly improved with PCA filtering in normal brain (P \u3c .05) and tumor (P \u3c .05). Tumor and brain BFs were significantly different from each other after PCA filtering with four principal components (P \u3c .05). CONCLUSIONS: PCA improved image CNR in vivo and reduced the measurement errors of BF, BV, and PS from simulation. A minimum of four principal components is recommended

Ohjaus ja dialoginen vuorovaikutus hoitotyössä

Hoitotyötä toteutetaan vuorovaikutuksessa asiakkaiden kanssa tavoitteena selvittää heidän hoitonsa tarve ja suunnitella sekä toteuttaa hoitoa asetettujen tavoitteiden suuntaan. Vuorovaikutuksella on merkitystä asiakkaiden hoidosta saamiinsa kokemuksiin. Kun ihmisten terveydentila muuttuu, aiheuttaa se usein haavoittuvuutta ja kriisin kokemuksia riippuen terveydentilan muutoksen vakavuudesta ja ihmisten omista persoonallisista vahvuuksista. Hoitajan tehtävänä on kohdata ihminen kokonaisvaltaisesti ja hänen kokemuksiaan huomioiden. Kun asiakas on mukana hoidossa päättämässä omaa hoitoaan koskevissa asioissa, niin sillä on todettu olevan vaikuttavuutta hoitotuloksiin ja myös hoidon kustannukset ovat laskeneet

Spearman’s rank correlations between CT perfusion parameters and histology measurement for control group (N = 18) animals.

<p>Spearman’s rank correlations between CT perfusion parameters and histology measurement for control group (N = 18) animals.</p

Examples of brain histology with pimonidazole.

<p>(a) 5 μm thick brain specimen stained for hypoxia (red arrows). (b) Zoomed area around the tumour (orange outline), pimonidazole-positive area (green outline), and necrotic area (red dashed line).</p