Las prescripciones curriculares y los procesos de programación de la enseñanza : Analizando algunas relaciones

El presente trabajo se enmarca en el Proyecto de Investigación denominado "Programación de la enseñanza en la escuela primaria: discursos y prácticas", aprobado en el Programa de Incentivos a la Investigación (H588). Nos interesa presentar en esta oportunidad un estado de avance de una línea de indagación que venimos desarrollando dentro del mencionado proyecto, referida a lo que en términos generales podríamos denominar las prescripciones curriculares. Es decir, nuestro interés está focalizado en analizar las prescripciones curriculares que se configuran y el carácter que a las mismas se les asigna en los diferentes niveles de concreción o especificación curricular. La programación de la enseñanza que estudiamos en nuestra investigación, entendida como un proceso progresivo de concreción de las intencionalidades educativas, puede ser analizada desde diferentes perspectivas. A los fines de esta presentación, priorizamos aquella que busca contextualizar las propuestas de clase de los maestros de la escuela primaria en el Diseño Curricular y en los Materiales de Desarrollo Curricular, prestándole atención a las prescripciones que se generan desde lo curricular y a la particular relectura que los docentes hacen de dichas prescripciones

Las prescripciones curriculares y los procesos de programación de la enseñanza : Analizando algunas relaciones

El presente trabajo se enmarca en el Proyecto de Investigación denominado "Programación de la enseñanza en la escuela primaria: discursos y prácticas", aprobado en el Programa de Incentivos a la Investigación (H588). Nos interesa presentar en esta oportunidad un estado de avance de una línea de indagación que venimos desarrollando dentro del mencionado proyecto, referida a lo que en términos generales podríamos denominar las prescripciones curriculares. Es decir, nuestro interés está focalizado en analizar las prescripciones curriculares que se configuran y el carácter que a las mismas se les asigna en los diferentes niveles de concreción o especificación curricular. La programación de la enseñanza que estudiamos en nuestra investigación, entendida como un proceso progresivo de concreción de las intencionalidades educativas, puede ser analizada desde diferentes perspectivas. A los fines de esta presentación, priorizamos aquella que busca contextualizar las propuestas de clase de los maestros de la escuela primaria en el Diseño Curricular y en los Materiales de Desarrollo Curricular, prestándole atención a las prescripciones que se generan desde lo curricular y a la particular relectura que los docentes hacen de dichas prescripciones

Las prescripciones curriculares y los procesos de programación de la enseñanza : Analizando algunas relaciones

El presente trabajo se enmarca en el Proyecto de Investigación denominado "Programación de la enseñanza en la escuela primaria: discursos y prácticas", aprobado en el Programa de Incentivos a la Investigación (H588). Nos interesa presentar en esta oportunidad un estado de avance de una línea de indagación que venimos desarrollando dentro del mencionado proyecto, referida a lo que en términos generales podríamos denominar las prescripciones curriculares. Es decir, nuestro interés está focalizado en analizar las prescripciones curriculares que se configuran y el carácter que a las mismas se les asigna en los diferentes niveles de concreción o especificación curricular. La programación de la enseñanza que estudiamos en nuestra investigación, entendida como un proceso progresivo de concreción de las intencionalidades educativas, puede ser analizada desde diferentes perspectivas. A los fines de esta presentación, priorizamos aquella que busca contextualizar las propuestas de clase de los maestros de la escuela primaria en el Diseño Curricular y en los Materiales de Desarrollo Curricular, prestándole atención a las prescripciones que se generan desde lo curricular y a la particular relectura que los docentes hacen de dichas prescripciones

Implications of Intercellular Signaling for Radiation Therapy: A Theoretical Dose-Planning Study

Purpose
Recent in vitro results have shown significant contributions to cell killing from signaling effects at doses that are typically used in radiation therapy. This study investigates whether these in vitro observations can be reconciled with in vivo knowledge and how signaling may have an impact on future developments in radiation therapy.
Methods and Materials
Prostate cancer treatment plans were generated for a series of 10 patients using 3-dimensional conformal therapy, intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy techniques. These plans were evaluated using mathematical models of survival following modulated radiation exposures that were developed from in vitro observations and incorporate the effects of intercellular signaling. The impact on dose-volume histograms and mean doses were evaluated by converting these survival levels into "signaling-adjusted doses" for comparison.
Results
Inclusion of intercellular communication leads to significant differences between the signalling-adjusted and physical doses across a large volume. Organs in low-dose regions near target volumes see the largest increases, with mean signaling-adjusted bladder doses increasing from 23 to 33 Gy in IMRT plans. By contrast, in high-dose regions, there is a small decrease in signaling-adjusted dose due to reduced contributions from neighboring cells, with planning target volume mean doses falling from 74 to 71 Gy in IMRT. Overall, however, the dose distributions remain broadly similar, and comparisons between the treatment modalities are largely unchanged whether physical or signaling-adjusted dose is compared. Conclusions Although incorporating cellular signaling significantly affects cell killing in low-dose regions and suggests a different interpretation for many phenomena, their effect in high-dose regions for typical planning techniques is comparatively small. This indicates that the significant signaling effects observed in vitro are not contradicted by comparison with clinical observations. Future investigations are needed to validate these effects in vivo and to quantify their ranges and potential impact on more advanced radiation therapy techniques.

A Novel Method of Evaluating Ureteropelvic Junction Obstruction: Dynamic Near Infrared Fluorescence Imaging Compared to Standard Modalities to Assess Urinary Obstruction in a Swine Model

Purpose: Dynamic near infrared fluorescence imaging of the urinary tract provides a promising way to diagnose ureteropelvic junction obstruction. Initial studies demonstrated the ability to visualize urine flow and peristalsis in great detail. We analyzed the efficacy of near infrared imaging in evaluating ureteropelvic junction obstruction, renal involvement and the anatomical detail provided compared to conventional imaging modalities. Materials and Methods: Ten swine underwent partial or complete unilateral ureteral obstruction. Groups were survived for the short or the long term. Imaging was performed with mercaptoacetyltriglycine diuretic renogram, magnetic resonance urogram, excretory urogram, ultrasound and near infrared imaging. Scoring systems for ureteropelvic junction obstruction were developed for magnetic resonance urogram and near infrared imaging. Physicians and medical students graded ureteropelvic junction obstruction based on magnetic resonance urogram and near infrared imaging results. Results: Markers of vascular and urinary dynamics were quantitatively consistent among control renal units. The same markers were abnormal in obstructed renal units with significantly different times of renal phase peak, start of pelvic phase and start of renal uptake. Such parameters were consistent with those obtained with mercaptoacetyltriglycine diuretic renography. Near infrared imaging provided live imaging of urinary flow, which was helpful in identifying the area of obstruction for surgical planning. Physicians and medical students categorized the degree of obstruction appropriately for fluorescence imaging and magnetic resonance urogram. Conclusions: Near infrared imaging offers a feasible way to obtain live, dynamic images of urine flow and ureteral peristalsis. Qualitative and quantitative parameters were comparable to those of conventional imaging. Findings support fluorescence imaging as an accurate, easy to use method of diagnosing ureteropelvic junction obstruction.

Multimodality Preoperative Planning and Postoperative Follow-up of a Hybrid Cardiac Intervention

We describe the case of a 59-year-old man who had aortic regurgitation and a hypoplastic aortic valve and for whom an echocardiography evaluation revealed a vascular tumor in the roof of the left atrium, which was suspected to be a hemangioma. After undergoing preoperative invasive catheter coronary angiography, echocardiography, and multislice computed tomography examinations, the patient underwent an aortic miniroot replacement. Intraoperative findings confirmed the findings of the preoperative evaluations. The tumor, although macroscopically verified as a hemangioma, was not resected because of the tumor's position and size, and the threat of uncontrollable bleeding. After an uneventful postoperative clinical course, a subsequent successful transcatheter coil occlusion of the coronary fistula from the left circumflex coronary artery was performed as an alternative to surgical resection of the tumor. This case emphasizes the future role of a multimodality hybrid approach for diagnosis, planning (different 2- and 3-dimensional imaging modalities), and treatment in the form of combining interventional (transcatheter) and surgical (open heart) techniques, which could optimize different treatment strategies. This approach could be further improved by increasing the installations of hybrid operating rooms.

Increasing Realism and Supporting Content Planning for Dynamic Scenes in a Mixed Reality System incorporating a Time-of-Flight Camera

For broadcasting purposes MIXED REALITY, the combination of real and virtual scene content, has become ubiquitous nowadays. Mixed Reality recording still requires expensive studio setups and is often limited to simple color keying. We present a system for Mixed Reality applications which uses depth keying and provides threedimensional mixing of real and artificial content. It features enhanced realism through automatic shadow computation which we consider a core issue to obtain realism and a convincing visual perception, besides the correct alignment of the two modalities and correct occlusion handling. Furthermore we present a possibility to support placement of virtual content in the scene. Core feature of our system is the incorporation of a TIME-OF-FLIGHT (TOF)-camera device. This device delivers real-time depth images of the environment at a reasonable resolution and quality. This camera is used to build a static environment model and it also allows correct handling of mutual occlusions between real and virtual content, shadow computation and enhanced content planning. The presented system is inexpensive, compact, mobile, flexible and provides convenient calibration procedures. Chroma-keying is replaced by depth-keying which is efficiently performed on the GRAPHICS PROCESSING UNIT (GPU) by the usage of an environment model and the current ToF-camera image. Automatic extraction and tracking of dynamic scene content is herewith performed and this information is used for planning and alignment of virtual content. An additional sustainable feature is that depth maps of the mixed content are available in real-time, which makes the approach suitable for future 3DTV productions. The presented paper gives an overview of the whole system approach including camera calibration, environment model generation, real-time keying and mixing of virtual and real content, shadowing for virtual content and dynamic object tracking for content planning.

Semiautomatic Cochleostomy Target and Insertion Trajectory Planning for Minimally Invasive Cochlear Implantation

A major component of minimally invasive cochlear implantation is atraumatic scala tympani (ST) placement of the electrode array. This work reports on a semiautomatic planning paradigm that uses anatomical landmarks and cochlear surface models for cochleostomy target and insertion trajectory computation. The method was validated in a human whole head cadaver model (n = 10 ears). Cochleostomy targets were generated from an automated script and used for consecutive planning of a direct cochlear access (DCA) drill trajectory from the mastoid surface to the inner ear. An image-guided robotic system was used to perform both, DCA and cochleostomy drilling. Nine of 10 implanted specimens showed complete ST placement. One case of scala vestibuli insertion occurred due to a registration/drilling error of 0.79 mm. The presented approach indicates that a safe cochleostomy target and insertion trajectory can be planned using conventional clinical imaging modalities, which lack sufficient resolution to identify the basilar membrane.

Computer Assisted Diagnosis and Treatment Planning of Femoroacetabular Impingement (FAI)

Femoroacetabular impingement (FAI) is a dynamic conflict of the hip defined by a pathological, early abutment of the proximal femur onto the acetabulum or pelvis. In the past two decades, FAI has received increasing focus in both research and clinical practice as a cause of hip pain and prearthrotic deformity. Anatomical abnormalities such as an aspherical femoral head (cam-type FAI), a focal or general overgrowth of the acetabulum (pincer-type FAI), a high riding greater or lesser trochanter (extra-articular FAI), or abnormal torsion of the femur have been identified as underlying pathomorphologies. Open and arthroscopic treatment options are available to correct the deformity and to allow impingement-free range of motion. In routine practice, diagnosis and treatment planning of FAI is based on clinical examination and conventional imaging modalities such as standard radiography, magnetic resonance arthrography (MRA), and computed tomography (CT). Modern software tools allow three-dimensional analysis of the hip joint by extracting pelvic landmarks from two-dimensional antero-posterior pelvic radiographs. An object-oriented cross-platform program (Hip2Norm) has been developed and validated to standardize pelvic rotation and tilt on conventional AP pelvis radiographs. It has been shown that Hip2Norm is an accurate, consistent, reliable and reproducible tool for the correction of selected hip parameters on conventional radiographs. In contrast to conventional imaging modalities, which provide only static visualization, novel computer assisted tools have been developed to allow the dynamic analysis of FAI pathomechanics. In this context, a validated, CT-based software package (HipMotion) has been introduced. HipMotion is based on polygonal three-dimensional models of the patient’s pelvis and femur. The software includes simulation methods for range of motion, collision detection and accurate mapping of impingement areas. A preoperative treatment plan can be created by performing a virtual resection of any mapped impingement zones both on the femoral head-neck junction, as well as the acetabular rim using the same three-dimensional models. The following book chapter provides a summarized description of current computer-assisted tools for the diagnosis and treatment planning of FAI highlighting the possibility for both static and dynamic evaluation, reliability and reproducibility, and its applicability to routine clinical use.

Indications and Frequency for the Use of Cone Beam Computed Tomography for Implant Treatment Planning in a Specialty Clinic

PURPOSE To analyze the indications and frequency for three-dimensional (3D) imaging for implant treatment planning in a pool of patients referred to a specialty clinic over a 3-year period. MATERIALS AND METHODS All patients who received dental implants between 2008 and 2010 at the Department of Oral Surgery and Stomatology at the University of Bern were included in the study. The influence of age, gender, and time of treatment (2008 to 2010) on the frequency of use of two-dimensional (2D) radiographic imaging modalities alone or in combination with 3D cone beam computed tomography (CBCT) scans was analyzed. Furthermore, the influence of the indication, location, and need for bone augmentation on the frequency of use of 2D imaging modalities alone or in combination with CBCT was evaluated. RESULTS In all, 1,568 patients (792 women and 776 men) received 2,279 implants. Overall, 633 patients (40.4%) were analyzed with 2D imaging procedures alone. CBCT was performed in 935 patients (59.6%). There was a statistically significant increase in CBCT between 2008 and 2010. Patients older than 55 years received a CBCT scan in addition to 2D radiographic imaging statistically significantly more often. Additional 3D imaging was most frequently performed in the posterior maxilla, whereas 2D radiographs alone exhibited the highest frequency in the anterior mandible. The combination of 2D with CBCT was used predominantly for implant placement with simultaneous or staged guided bone regeneration or sinus elevation. CONCLUSION Based on these findings from a specialty clinic, the use of additional CBCT imaging for implant treatment planning is influenced by the indication, location, local anatomy (including the need for bone augmentation), and the age of the patient.

Improving Cervical Cancer Nodal Boost Radiation Therapy by Quantifying Uncertainties and Exploring Advanced Radiation Therapy Modalities

Radiation therapy for patients with intact cervical cancer is frequently delivered using primary external beam radiation therapy (EBRT) followed by two fractions of intracavitary brachytherapy (ICBT). Although the tumor is the primary radiation target, controlling microscopic disease in the lymph nodes is just as critical to patient treatment outcome. In patients where gross lymphadenopathy is discovered, an extra EBRT boost course is delivered between the two ICBT fractions. Since the nodal boost is an addendum to primary EBRT and ICBT, the prescription and delivery must be performed considering previously delivered dose. This project aims to address the major issues of this complex process for the purpose of improving treatment accuracy while increasing dose sparing to the surrounding normal tissues. Because external beam boosts to involved lymph nodes are given prior to the completion of ICBT, assumptions must be made about dose to positive lymph nodes from future implants. The first aim of this project was to quantify differences in nodal dose contribution between independent ICBT fractions. We retrospectively evaluated differences in the ICBT dose contribution to positive pelvic nodes for ten patients who had previously received external beam nodal boost. Our results indicate that the mean dose to the pelvic nodes differed by up to 1.9 Gy between independent ICBT fractions. The second aim is to develop and validate a volumetric method for summing dose of the normal tissues during prescription of nodal boost. The traditional method of dose summation uses the maximum point dose from each modality, which often only represents the worst case scenario. However, the worst case is often an exaggeration when highly conformal therapy methods such as intensity modulated radiation therapy (IMRT) are used. We used deformable image registration algorithms to volumetrically sum dose for the bladder and rectum and created a voxel-by-voxel validation method. The mean error in deformable image registration results of all voxels within the bladder and rectum were 5 and 6 mm, respectively. Finally, the third aim explored the potential use of proton therapy to reduce normal tissue dose. A major physical advantage of protons over photons is that protons stop after delivering dose in the tumor. Although theoretically superior to photons, proton beams are more sensitive to uncertainties caused by interfractional anatomical variations, and must be accounted for during treatment planning to ensure complete target coverage. We have demonstrated a systematic approach to determine population-based anatomical margin requirements for proton therapy. The observed optimal treatment angles for common iliac nodes were 90° (left lateral) and 180° (posterior-anterior [PA]) with additional 0.8 cm and 0.9 cm margins, respectively. For external iliac nodes, lateral and PA beams required additional 0.4 cm and 0.9 cm margins, respectively. Through this project, we have provided radiation oncologists with additional information about potential differences in nodal dose between independent ICBT insertions and volumetric total dose distribution in the bladder and rectum. We have also determined the margins needed for safe delivery of proton therapy when delivering nodal boosts to patients with cervical cancer.

Multimodal non-rigid image registration methods for therapy and surgery planning

La planificación pre-operatoria se ha convertido en una tarea esencial en cirugías y terapias de marcada complejidad, especialmente aquellas relacionadas con órgano blando. Un ejemplo donde la planificación preoperatoria tiene gran interés es la cirugía hepática. Dicha planificación comprende la detección e identificación precisa de las lesiones individuales y vasos así como la correcta segmentación y estimación volumétrica del hígado funcional. Este proceso es muy importante porque determina tanto si el paciente es un candidato adecuado para terapia quirúrgica como la definición del abordaje a seguir en el procedimiento. La radioterapia de órgano blando es un segundo ejemplo donde la planificación se requiere tanto para la radioterapia externa convencional como para la radioterapia intraoperatoria. La planificación comprende la segmentación de tumor y órganos vulnerables y la estimación de la dosimetría. La segmentación de hígado funcional y la estimación volumétrica para planificación de la cirugía se estiman habitualmente a partir de imágenes de tomografía computarizada (TC). De igual modo, en la planificación de radioterapia, los objetivos de la radiación se delinean normalmente sobre TC. Sin embargo, los avances en las tecnologías de imagen de resonancia magnética (RM) están ofreciendo progresivamente ventajas adicionales. Por ejemplo, se ha visto que el ratio de detección de metástasis hepáticas es significativamente superior en RM con contraste Gd–EOB–DTPA que en TC. Por tanto, recientes estudios han destacado la importancia de combinar la información de TC y RM para conseguir el mayor nivel posible de precisión en radioterapia y para facilitar una descripción precisa de las lesiones del hígado. Con el objetivo de mejorar la planificación preoperatoria en ambos escenarios se precisa claramente de un algoritmo de registro no rígido de imagen. Sin embargo, la gran mayoría de sistemas comerciales solo proporcionan métodos de registro rígido. Las medidas de intensidad de voxel han demostrado ser criterios de similitud de imágenes robustos, y, entre ellas, la Información Mutua (IM) es siempre la primera elegida en registros multimodales. Sin embargo, uno de los principales problemas de la IM es la ausencia de información espacial y la asunción de que las relaciones estadísticas entre las imágenes son homogéneas a lo largo de su domino completo. La hipótesis de esta tesis es que la incorporación de información espacial de órganos al proceso de registro puede mejorar la robustez y calidad del mismo, beneficiándose de la disponibilidad de las segmentaciones clínicas. En este trabajo, se propone y valida un esquema de registro multimodal no rígido 3D usando una nueva métrica llamada Información Mutua Centrada en el Órgano (Organ-Focused Mutual Information metric (OF-MI)) y se compara con la formulación clásica de la Información Mutua. Esto permite mejorar los resultados del registro en áreas problemáticas incorporando información regional al criterio de similitud, beneficiándose de la disponibilidad real de segmentaciones en protocolos estándares clínicos, y permitiendo que la dependencia estadística entre las dos modalidades de imagen difiera entre órganos o regiones. El método propuesto se ha aplicado al registro de TC y RM con contraste Gd–EOB–DTPA así como al registro de imágenes de TC y MR para planificación de radioterapia intraoperatoria rectal. Adicionalmente, se ha desarrollado un algoritmo de apoyo de segmentación 3D basado en Level-Sets para la incorporación de la información de órgano en el registro. El algoritmo de segmentación se ha diseñado específicamente para la estimación volumétrica de hígado sano funcional y ha demostrado un buen funcionamiento en un conjunto de imágenes de TC abdominales. Los resultados muestran una mejora estadísticamente significativa de OF-MI comparada con la Información Mutua clásica en las medidas de calidad de los registros; tanto con datos simulados (p<0.001) como con datos reales en registro hepático de TC y RM con contraste Gd– EOB–DTPA y en registro para planificación de radioterapia rectal usando OF-MI multi-órgano (p<0.05). Adicionalmente, OF-MI presenta resultados más estables con menor dispersión que la Información Mutua y un comportamiento más robusto con respecto a cambios en la relación señal-ruido y a la variación de parámetros. La métrica OF-MI propuesta en esta tesis presenta siempre igual o mayor precisión que la clásica Información Mutua y consecuentemente puede ser una muy buena alternativa en aplicaciones donde la robustez del método y la facilidad en la elección de parámetros sean particularmente importantes. Abstract Pre-operative planning has become an essential task in complex surgeries and therapies, especially for those affecting soft tissue. One example where soft tissue preoperative planning is of high interest is liver surgery. It involves the accurate detection and identification of individual liver lesions and vessels as well as the proper functional liver segmentation and volume estimation. This process is very important because it determines whether the patient is a suitable candidate for surgical therapy and the type of procedure. Soft tissue radiation therapy is a second example where planning is required for both conventional external and intraoperative radiotherapy. It involves the segmentation of the tumor target and vulnerable organs and the estimation of the planned dose. Functional liver segmentations and volume estimations for surgery planning are commonly estimated from computed tomography (CT) images. Similarly, in radiation therapy planning, targets to be irradiated and healthy and vulnerable tissues to be protected from irradiation are commonly delineated on CT scans. However, developments in magnetic resonance imaging (MRI) technology are progressively offering advantages. For instance, the hepatic metastasis detection rate has been found to be significantly higher in Gd–EOB–DTPAenhanced MRI than in CT. Therefore, recent studies highlight the importance of combining the information from CT and MRI to achieve the highest level of accuracy in radiotherapy and to facilitate accurate liver lesion description. In order to improve those two soft tissue pre operative planning scenarios, an accurate nonrigid image registration algorithm is clearly required. However, the vast majority of commercial systems only provide rigid registration. Voxel intensity measures have been shown to be robust measures of image similarity, and among them, Mutual Information (MI) is always the first candidate in multimodal registrations. However, one of the main drawbacks of Mutual Information is the absence of spatial information and the assumption that statistical relationships between images are the same over the whole domain of the image. The hypothesis of the present thesis is that incorporating spatial organ information into the registration process may improve the registration robustness and quality, taking advantage of the clinical segmentations availability. In this work, a multimodal nonrigid 3D registration framework using a new Organ- Focused Mutual Information metric (OF-MI) is proposed, validated and compared to the classical formulation of the Mutual Information (MI). It allows improving registration results in problematic areas by adding regional information into the similitude criterion taking advantage of actual segmentations availability in standard clinical protocols and allowing the statistical dependence between the two modalities differ among organs or regions. The proposed method is applied to CT and T1 weighted delayed Gd–EOB–DTPA-enhanced MRI registration as well as to register CT and MRI images in rectal intraoperative radiotherapy planning. Additionally, a 3D support segmentation algorithm based on Level-Sets has been developed for the incorporation of the organ information into the registration. The segmentation algorithm has been specifically designed for the healthy and functional liver volume estimation demonstrating good performance in a set of abdominal CT studies. Results show a statistical significant improvement of registration quality measures with OF-MI compared to MI with both simulated data (p<0.001) and real data in liver applications registering CT and Gd–EOB–DTPA-enhanced MRI and in registration for rectal radiotherapy planning using multi-organ OF-MI (p<0.05). Additionally, OF-MI presents more stable results with smaller dispersion than MI and a more robust behavior with respect to SNR changes and parameters variation. The proposed OF-MI always presents equal or better accuracy than the classical MI and consequently can be a very convenient alternative within applications where the robustness of the method and the facility to choose the parameters are particularly important.

Microspheres for liver radiomicrospheres therapy and planning

Liver cancer accounts for nearly 10% of all cancers in the US. Intrahepatic Arterial Radiomicrosphere Therapy (RMT), also known as Selective Internal Radiation Treatment (SIRT), is one of the evolving treatment modalities. Successful patient clinical outcomes require suitable treatment planning followed by delivery of the microspheres for therapy. The production and in vitro evaluation of various polymers (PGCD, CHS and CHSg) microspheres for a RMT and RMT planning are described. Microparticles with a 30±10 µm size distribution were prepared by emulsion method. The in vitro half-life of the particles was determined in PBS buffer and porcine plasma and their potential application (treatment or treatment planning) established. Further, the fast degrading microspheres (≤ 48 hours in vitro half-life) were labeled with 68Ga and/or 99mTc as they are suitable for the imaging component of treatment planning, which is the primary emphasis of this dissertation. Labeling kinetics demonstrated that 68Ga-PGCD, 68Ga-CHSg and 68Ga-NOTA-CHSg can be labeled with more than 95% yield in 15 minutes; 99mTc-PGCD and 99mTc-CHSg can also be labeled with high yield within 15-30 minutes. In vitro stability after four hours was more than 90% in saline and PBS buffer for all of them. Experiments in reconstituted hemoglobin lysate were also performed. Two successful imaging (RMT planning) agents were found: 99mTc-CHSg and 68Ga-NOTA-CHSg. For the 99mTc-PGCD a successful perfusion image was obtained after 10 minutes, however the in vivo degradation was very fast (half-life), releasing the 99mTc from the lungs. Slow degrading CHS microparticles (> 21 days half-life) were modified with p-SCN-b-DOTA and labeled with 90 Y for production of 90Y-DOTA-CHS. Radiochemical purity was evaluated in vitro and in vivo showing more than 90% stability after 72 and 24 hours respectively. All agents were compared to their respective gold standards (99mTc-MAA for 68Ga-NOTA-CHSg and 99m Tc-CHSg; 90Y-SirTEX for 90Y-DOTA-CHS) showing superior in vivo stability. RMT and RMT planning agents (Therapy, PET and SPECT imaging) were designed and successfully evaluated in vitro and in vivo.

Microspheres for Liver Radiomicrospheres Therapy and Planning

Liver cancer accounts for nearly 10% of all cancers in the US. Intrahepatic Arterial Radiomicrosphere Therapy (RMT), also known as Selective Internal Radiation Treatment (SIRT), is one of the evolving treatment modalities. Successful patient clinical outcomes require suitable treatment planning followed by delivery of the microspheres for therapy. The production and in vitro evaluation of various polymers (PGCD, CHS and CHSg) microspheres for a RMT and RMT planning are described. Microparticles with a 30±10 µm size distribution were prepared by emulsion method. The in vitro half-life of the particles was determined in PBS buffer and porcine plasma and their potential application (treatment or treatment planning) established. Further, the fast degrading microspheres (≤ 48 hours in vitro half-life) were labeled with 68Ga and/or 99mTc as they are suitable for the imaging component of treatment planning, which is the primary emphasis of this dissertation. Labeling kinetics demonstrated that 68Ga-PGCD, 68Ga-CHSg and 68Ga-NOTA-CHSg can be labeled with more than 95% yield in 15 minutes; 99mTc-PGCD and 99mTc-CHSg can also be labeled with high yield within 15-30 minutes. In vitro stability after four hours was more than 90% in saline and PBS buffer for all of them. Experiments in reconstituted hemoglobin lysate were also performed. Two successful imaging (RMT planning) agents were found: 99mTc-CHSg and 68Ga-NOTA-CHSg. For the 99mTc-PGCD a successful perfusion image was obtained after 10 minutes, however the in vivo degradation was very fast (half-life), releasing the 99mTc from the lungs. Slow degrading CHS microparticles (> 21 days half-life) were modified with p-SCN-b-DOTA and labeled with 90Y for production of 90Y-DOTA-CHS. Radiochemical purity was evaluated in vitro and in vivo showing more than 90% stability after 72 and 24 hours respectively. All agents were compared to their respective gold standards (99mTc-MAA for 68Ga-NOTA-CHSg and 99mTc-CHSg; 90Y-SirTEX for 90Y-DOTA-CHS) showing superior in vivo stability. RMT and RMT planning agents (Therapy, PET and SPECT imaging) were designed and successfully evaluated in vitro and in vivo.