Bone Quality Research Lab (Kazakia Lab)

Bone Quality Research - microCT, HR-pQCT, and Fourier transform infrared (FTIR) spectroscopy

Our main research interest is the characterization of bone structure and composition in osteoporosis and other disease states using both ex vivo and in vivo high resolution imaging techniques. Specifically, we are developing techniques in micro computed tomography (microCT), high resolution peripheral quantitative CT (HR-pQCT), and Fourier transform infrared (FTIR) spectroscopy for the assessment of bone quality. As a part of the Musculoskeletal Quantitative Imaging Research (MQIR) group in the Department of Radiology and Biological Imaging at UCSF, we enjoy a rich, collaborative environment working closely with researchers, clinicians, and students. We are committed to the training and education of postdoctoral fellows, residents, and students (medical, graduate, undergraduate, and high school) interested in pursuing a career in musculoskeletal research. Our research is supported by the NIH and by intramural UCSF funding.

People

Galateia J. Kazakia, PhDGalateia J. Kazakia, PhD
Director
Assistant Professor in Residence

Dr. Kazakia received a B.S. in Mechanical Engineering from Cornell University in 1995. After working as a Biomechanical Design Engineer at the Hospital for Special Surgery in New York, she joined the Orthopaedic Biomechanics Lab at UC Berkeley and earned her Ph.D. in Mechanical Engineering (major fields: Bioengineering & Materials) in 2004. She was awarded an NIH postdoctoral fellowship to develop bone imaging techniques, performing this work in the Musculoskeletal Quantitative Imaging Research group at UCSF. Dr. Kazakia joined the UCSF Department of Radiology and Biomedical Imaging as Assistant Professor in Residence in 2009.

Staff

  • Celestine Fry: Administrative Assistant
  • Melissa Guan: Clinical Research Coordinator
  • Neha Kidambi: Undergraduate Student Researcher (URAP), UC Berkeley
  • Susan Lin: Financial Analyst
  • Courtney Pasco: Undergraduate Student Researcher (URAP), UC Berkeley
  • Grace Jun, Clinical Research Coordinator
  • Melis Yilmaz: Undergraduate Student Researcher (URAP), UC Berkeley

Alumni

  • Gregory Bernstein: Undergraduate Student Researcher (URAP) 
  • Julio Carballido-Gamio: Senior Scientist 
  • Karen Cheng: Undergraduate Student Researcher (QUEST/URAP)
  • Sam Cheung: Undergraduate Student Researcher (URAP)
  • Harsh Goel: Undergraduate Student Researcher (URAP)
  • Jasmine Nirody: Graduate Student Researcher (UC Berkeley)
  • Joyce Pang: Undergraduate Student Researcher (URAP)
  • Robin Parrish: Undergraduate Student Researcher (UC Berkeley)
  • Kiranjit Sekhon: Undergraduate Student Researcher (URAP)
  • Swetha Shanbhag: Undergraduate Student Researcher (URAP)
  • Hsin-Wei Shen: Specialist
  • Derek Speer: Undergraduate Student Researcher (URAP)
  • Willy Tjong: Staff Research Associate
  • Yang Zhao: Undergraduate Student Researcher

Publications

Bone Quality Research Lab Opportunities

Internships

We have student research assistant positions available for the semester, summer, or for longer term. In particular, we look for highly motivated students with programming experience to help with advanced image processing, or with lab experience to help with cadaver and animal specimen experiments. The students will be trained in all necessary procedures and exposed to both basic science and clinical aspects of musculoskeletal research. Students will also have the opportunity to work closely with radiologists, orthopaedic surgeons and imaging scientists. Potential applicants are encouraged to review the following training programs, in which we actively participate:

Available Positions

-Employment Opportunities for staff positions are posted through the UCSF Department of Human Resources.

-Post-Doctoral Research Fellow in Musculoskeletal Imaging (Posted: 11/09/16)

Research Projects 

HR-pQCT in vivo bone quality assessment

Accurate quantification of bone microarchitecture is significant in understanding bone mechanics and response to disease or treatment. High-resolution peripheral quantitative computed tomography (HR-pQCT) allows for the quantification of trabecular and cortical structure in vivo, with the capability of generating images at multiple resolutions. The aim of this project is to characterize the effect of resolution on structural measures of trabecular and cortical bone and to determine accuracy in reference to micro-CT (µCT), the gold standard for bone microarchitecture quantification.


Figure: Representative images of the trabecular segmentation for both µCT and HR-pQCT images. A) Grayscale images acquired by the respective scanners. B) Trabecular segmentation of a single slice. C) 3D representation of the trabecular volume.

A novel method for quantifying cortical pore topology

Osteonal clustering and merging is increased in hip fracture cases, suggesting that the structural realignment of porosity may be a mechanism of fracture by means of altered local strain and stress fields within cortical tissue. We therefore believe the investigation of pore topology is important to estimating the effects of age, disease, and therapeutic interventions on fracture risk. This project develops a pore topology analysis technique which provides data pertinent to pore clustering, realignment, and interconnectedness. The technique utilizes a skeletonization routine to deconstruct the cortical pore network into individual elements, allowing for the classification of each element as either a plate or a rod. From the skeletonized image, parameters of pore structure and topology can be quantified.


Figure: Pore topology analysis of a tibial cross-section allows for calculation of parameters describing cortical pore structure.

Effects of reduced weight-bearing on skeletal geometry, micro-structure, strength

Significant bone is a common consequence of immobilization or restricted weight-bearing. Previous studies investigating bone loss in this context have focused on changes in bone mineral density (BMD). However, since cortical and trabecular microstructure contribute significantly to bone strength, we quantify and evaluate changes in microstructural and biomechanical parameters at the distal tibia during and after a period of non-weight-bearing. A long-term clinical focus of this research is to facilitate the development of targeted countermeasures to prevent bone loss.

MicroCT quantification of bone composition

The contribution of bonetissuequality to bone mechanics is not captured by bone mineral density or architectural measures. Assessment of bone tissue mineral density (TMD) may be critical to our understanding of bone biomechanics. Although high-resolution 3D assessment of TMD has been performed using synchrotron radiation microcomputed tomography (SRμCT), this imaging modality is not widely available. As conventional desktop μCT systems are far more easily accessed, we compare μCT-based measurements of bone mineral content, TMD, and structure measures to those obtained by SRμCT.


Figure: Comparison of μCT and SR μCT. Top: μCT (left) and SRμCT (right) images of a trabecular bone specimen. Bottom: Histograms of TMD data for a single sample.

Mineralization abnormalities in a mouse model of fibrous dysplasia

It is known that activation of the Gs G-protein coupled receptor (GPCR) pathway in osteoblasts can lead to significant increases in trabecular bone formation. However, the effects of constitutive Gs signaling on bone tissue quality are not known. Using Fourier transform infrared (FTIR) spectroscopy and synchrotron radiation μCT (SRμCT), we evaluate the bone composition of double transgenic mice that exhibit osteoblast-specific constitutive Gs signaling activity. Our findings demonstrate that Gs activity in osteoblasts leads to the deposition of immature bone tissue with reduced mineralization.


Figure: Evaluation of bone quality in double transgenic (DT) compared to wildtype (WT) mice. Top:Full bone renderings (inset) and detailed sections from mid-diaphysis of femurs from 3-week old wildtype (left) and double transgenic (right) mice. Bottom: Mid-diaphyseal cross-section of a 9-week old double transgenic mouse (right) and SRμCT data (left) show a decrease in mineralized bone tissue and a disordered mineralization pattern.