Neuroradiology Clinical Division Research

Dr. Soonmee Cha, MD, Director

Brain tumors, called Glioblastoma Multiforme (GBMs) are the most common adult primary brain tumors. They can occur at any age but are more common in older patients. These tumors are diagnosed with imaging studies and a tumor biopsy. Currently, the use of a contrast-enhanced MRI is a sensitive means of delineating anatomic and structural features of brain tumors. This technology, however, often fails to detect subtle tumor infiltration beyond the contrast-enhancing margin of the tumor or differentiate the active tumor from therapy-related brain injury.

MR perfusion and map of brain tumor.

At UCSF’s Neuroradiology Research Laboratory, Director, Dr. Soonmee Cha and her colleagues are studying the potential of anatomic and physiologic MRI as useful tools for improved GBM classification, benefits for cancer therapy monitoring, and more accurate surgery planning to help surgeons and their patients.

Dr. Cha and her team have validated physiologic variables by directly correlating them with the study of microscopic changes or abnormalities in tissues of the tumor specimen obtained through image-guided stereotactic biopsy. The team is also exploring the benefits of combining imaging with genetic analysis of GBM. Researchers are trying to better understand the possible implications for apparent self-renewing brain tumors.

MR images of a Glioblastoma Multiforme:

1. Fluid-attenuated inversion recovery image shows a bright tumor adjacent to the right lateral ventricle.
2. Post-contrast SPGR T1-weighted image shows heterogeneous enhancement within the tumor.
3. Dynamic susceptibility-weighted contrast-enhanced perfusion MR image shows markedly increased vascularity (red) within the tumor due to underlying angiogenesis.
4. Dynamic contrast-enhanced permeability image shows a marked increase in vessel leakiness (red and yellow) within the central aspect of the tumor.

The hypothesis is that neural stem cells in the subventricular zone (SVZ) of the human brain, where self-renewing neurons in the adult brain are located, maybe the cellular origin of GBM brain tumors. To explore this hypothesis, the features of GBM tumors in specific relation to the SVZ have been analyzed, and this research is continuing with an analysis of genetic markers, such as methylation and mRNA.

Physicians are welcome to contact Dr. Soonmee Cha for further information at (415) 353-9301 or by email at [email protected].

Dr. Christopher P. Hess, MD, PhD, Director

Standard anatomical imaging in degenerative disorders of the brain, including dementia, affects a growing number of patients across an aging population. With 20 years of experience in MRI engineering, Dr. Hess and his group develop and employ new MRI techniques to study the process of neurodegeneration in disorders, including Huntington's disease, Alzheimer's disease, and Parkinsonian disorders. Ultra-high field 7 tesla MRI, diffusion MRI, quantitative susceptibility mapping, and mathematical morphometry techniques are currently being explored in his laboratory. Through multi modality imaging and advanced image analysis techniques, the goal of this work is to make possible more accurate diagnosis and to monitor the effect of treatments under development using imaging. Dr. Hess' group excels at translating state-of-the-art research techniques to practical imaging in clinical patients, and the advanced imaging techniques developed by his group are also currently being used to more accurately characterize brain tumors, study neurovascular disorders, and understand plasticity in the newborn brain.

High-resolution imaging using 7 tesla MRI. The left images show atrophy and iron accumulation within the right basal ganglia of a patient with an atypical movement disorder compared to a normal control subject. The right images compare the right hippocampus of a patient with epilepsy acquired using 7 tesla (left) and 3 tesla (right) MRI.

Physicians are welcome to contact Dr. Christopher Hess for further information at (415) 514-4385 or by email at [email protected].

Dr. Sri Nagarajan, PhD, Director

Functional Brain Imaging

The Biomagnetic Imaging Laboratory (BIL) is a shared clinical and research facility in the Department of Radiology and Biomedical Imaging at UCSF. The program is focused on improving non-invasive functional brain imaging methods to develop a better understanding of the dynamics of brain networks associated with complex human behaviors, such as speech, language, memory, and attention. The laboratory conducts basic and clinical research on brain function using multiple brain imaging modalities, including magnetoencephalographic imaging (MEGI), functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation (TMS), and psychophysics.

Ongoing Functional Brain Imaging research projects include:

• Imaging the plasticity of the brain associated with learning, disease, recovery, and therapeutic interventions
  • Ongoing clinical studies are in patients with autism, brain tumors, dementias, dystonia, epilepsy, neurodevelopmental disorders, Parkinson’s disease, schizophrenia, stroke, tinnitus and traumatic brain injury
• Imaging speech and language processing and speech motor control of speech
• Developing machine learning algorithms and tools for:
  • Multimodal functional brain imaging,
  • Imaging structural and functional connectivity
  • Brain computer interfaces (BCI)
• Developing novel clinical applications for MEGI and TMS

Functional Brain Images:

The patient experienced word finding and word production difficulties. The MEGI study at BIL found a lesion located close to the auditory cortex in the right hemisphere and in close proximity to brain regions that process speech and language (red icon).

The patient experienced facial twitching, numbness, and arm spasms, with some word-finding difficulties. MEGI found a tumor located in the vicinity of auditory cortex, close to somatosensory cortex for the lip (red icon).

Clinical Services Offered in the Biomagnetic Imaging Lab

Our laboratory provides clinical services for referring physicians and their patients, including:

• Functional brain mapping in patients with brain tumors and arteriovenous malformations (AVMs),
• Epileptic zone localization in patients with epilepsy

Functional brain mapping services are important and clinically useful for mapping sensory, motor, and language areas prior to neurosurgical procedures. The team offers and conducts epileptic zone localization studies in patients with seizure disorders or epilepsy to identify causes of epileptic activity and potential seizure triggers, evaluate patients, and contribute to preparations for epilepsy surgery.

Patient with medically intractable epilepsy. Conventional MR imaging shows an abnormal signal in the right hippocampus (left and middle) consistent with mesial temporal sclerosis. Magnetic source imaging (Magnetoencephalography or MEG) demonstrates multiple seizure foci (white triangles) adjacent to pathology. Following surgical resection, the patient became seizure free.

Physicians seeking more information or wishing to order a study for a patient, please call the Biomagnetic Imaging Laboratory at (415) 476-6888.  Physicians are welcome to contact Dr. Nagarajan at (415) 476-4982 or email him at [email protected].

More information is available at the Biomagnetic Imaging Laboratory site.

 Dr. David M. Wilson, MD, PhD, Director

The research goal within the Molecular Imaging Research group, led by Dr. David Wilson, is to understand better the molecular mechanisms of the brain, in both health and disease.  Cells within the brain communicate with each other using simple molecules, and maintain normal functioning by accumulating large quantities of antioxidants including Vitamin C.

The UCSF team has developed methods to make images of brain antioxidants, which are depleted in aging, stroke, and neurodegenerative diseases including Alzheimer's disease.

Dr. Wilson’s team also has the goal of developing new ways to detect harmful pro-oxidant molecules themselves, using positron emission tomography (PET), a technology commonly used in cancer detection.  These methods will allow us to detect oxidative damage in patients non-invasively, and therefore monitor the therapeutic efficacy of our interventions.  As we develop more methods to detect the basic chemistry of the normal and abnormal brain, our approaches to treatment will be increasingly patient-centered.

Physicians are welcome to contact Dr. David Wilson for more information at [email protected] or telephone (415) 514-6229.

Dr. Pratik Mukherjee, MD, PhD, Director

Dr. Pratik Mukherjee's research focuses on the technical development of advanced imaging methods and their application to cognitive neuroscience for mapping structure and function in the human brain.  In particular, diffusion tensor imaging (DTI) is a cutting edge MRI technique proven useful for assessing the development and integrity of white matter and for mapping axonal fiber pathways.  Dr. Mukherjee made many of the initial observations of human white matter development in newborns and children using this technique.  He also led the development of more advanced methods known collectively as “high angular resolution diffusion imaging” (HARDI) for surmounting the limitations of DTI for characterizing regions of complex white matter architecture. 

Traumatic Brain Injury

Currently, Dr. Mukherjee's primary clinical research effort is the study of traumatic brain injury (TBI) using advanced MR imaging techniques, including DTI.  Dr. Mukherjee has also made novel scientific findings about the organization of white matter in the normal adult brain using multivariate statistical analyses of group DTI data.  More recently, Dr. Mukherjee has also employed functional connectivity mapping based on resting state fMRI and MEG for basic and clinical neuroscience applications.  Diffusion tractography and resting state fMRI/MEG technology have been used in Dr. Mukherjee’s lab to map the structural and functional “connectome” of the human brain, both to study normal brain organization as well as pathologic conditions such as brain malformations and brain injury.

1. Initial resting state MEG scan after mild TBI.
2. Resting state MEG scan 26 months later showing improved connections with time.

Dr. A. James Barkovich, MD, Director

Pediatric Neuroradiology Research is led by Dr. A. James Barkovich. Dr. Barkovich has been doing research in this field for 30 years.  He is a world leader in imaging of newborn children, children with epilepsy, infants and children with developmental brain malformations, and inborn errors of metabolism and has authored many papers on all of these subjects.  His research in these fields has been funded by the National Institutes of Health for more than 20 years, with the work leading to more than 400 peer reviewed publications in the medical and scientific literature.  He has won research awards from the United Cerebral Palsy Research and Education Foundation, the American Society of Neuroradiology, the Swiss-German-Austrian Child Neurology Society and the Radiological Society of North America, and has been recognized as the Faculty Clinical Research Lecturer at UCSF.  Dr. Barkovich’s textbook on pediatric neuroradiology, called Pediatric Neuroimaging, is now in its 5th edition and is generally considered to be the definitive textbook in the field.  Dr. Barkovich has close collaborations in his research and clinical work with members of the departments of Child Neurology, Pediatric Neurosurgery, and Neonatology, as well as a strong team of imaging scientists led by Dr. Duan Xu.  

Together with Dr. Xu, Dr. Barkovich uses state of the art MRI techniques to study the process of normal brain development.  This knowledge allows them to understand better abnormalities seen on MR studies of newborn and infant patients. Analysis of myelination, (the development of myelin sheaths around nerve fibers of the central nervous system in order to increase the speed of transmission of nerve signals), is one area of particular research interest.  The processing speed of a brain is determined, in large part, by the myelination around the nerves in the brain. When nerves are myelinated properly, messages and neuronal signals are transmitted through the brain more effectively. Various diseases may demyelinate the white matter, resulting in brain dysfunction.

Pediatric neuroradiology research includes:

Abnormal brain development

High resolution MRI and diffusion tensor MR imaging (DTI), and functional MRI are used to investigate the brain anatomy, function and connectivity. These findings are correlated with genetic testing to help understand of how abnormal expression of many different genes affects brain function; more importantly, we are trying to find out how development of the brain is affected by abnormal gene expression and how abnormal development can be (1) prevented and (2) improved.  Brain malformations being studied include anomalies of brain connections, malformations of formation of the forebrain (cerebrum), and malformations of the midbrain and hindbrain (brain stem and cerebellum).  Dr. Barkovich is the primary author of the most widely cited classifications of these malformations.

Neonatal brain injury

Standard MR imaging (MRI), MR spectroscopy (MRS), diffusion tensor MR imaging (DTI, to show connectivity), and cerebral blood flow imaging are utilized to assess encephalopathic neonates (who have difficulty with respiration, depressed tone and reflexes, subnormal level of consciousness and may have seizures) in order to find and precisely locate neonatal brain injury and determine its severity.  Dr. Barkovich and Dr. Xu and their collaborators have built special MR compatible transport tables and incubators and special imaging coils to to get the best images with maximum safety. These babies have been followed for many years, and we are determining what the early imaging findings mean in regard to neurodevelopmental outcomes later in childhood and adolescence.  

Prematurely born neonates

Many prematurely born infants ultimately have neurodevelopmental disabilities. UCSF Pediatric Neuroradiology researchers use state of the art MRI, MRS, DTI and fMRI to assess the brains of prematurely born neonates in order to detect subtle abnormalities that can impact development and provide information to primary care and neonatal specialists and parents.  We are working with Neonatologists, Child Neurologists, and Child Psychologists to determine which MRI findings determine the child’s outcomes and use MRI to help determine which treatments are most effective.  

Fetal Brain and Spine

Most pregnant women have ultrasound studies of their fetuses to make sure that they are developing normally.  Sometimes fetal ultrasound examinations do not show everything clearly or show findings that may or may not be abnormal.  In these situations, MRI of the fetus can be very helpful.  MRI shows the fetal brain and spine much more clearly than ultrasound and is very helpful to show whether the ultrasound findings are real, and might cause a problem, or when they are a “false alarm”.  MRI uses no harmful radiation and no sedation is necessary for the mother or the fetus.  

Physicians, please feel free to call Dr. A. James Barkovich for further information at (415) 353-1668 / 1537 or e-mail [email protected].

Dr. Orit Glenn, MD, Director

The Fetal Neuroimaging Program is led by Dr. Orit Glenn, M.D. This program develops advanced imaging techniques to study normal and abnormal fetal brain development. Fetal MR imaging is used to help answer questions about fetal anatomic structure before birth when it can be a helpful in making medical decisions or planning critical care. The clinical scientists use specialized real–time MR techniques to detect various congenital (inherited) abnormalities and correlate these with childhood development. 

These imaging studies can help parents and doctors make decisions during pregnancy and prepare in advance for challenges that the child and family may face. The Fetal Neuroimaging Research Program is a collaborative effort of MR scientists working with obstetricians, perinatologists, child neurologists, geneticists, pediatric neurosurgeons, fetal treatment surgeons, and neonatologists. By developing new and improved fetal MR techniques, (such as the generation of 3D high resolution images, fetal diffusion weighted imaging, and fetal diffusion tensor imaging,) changes in brain measurements, shape, and dimension as well as changes in the microstructure of white matter can be quantified. These techniques contribute to understanding and clinical decision-making regarding a wide range of neuro-developmental disorders.

Learn more about Fetal Neuroimaging.

For physicians to discuss this further, please email Dr. Orit Glenn, MD, at [email protected].

Doctors Cynthia Chin, MD, William Dillon, MD, Christopher Hess, MD, PhD, and Sharmila Majumdar, PhD

The Spine Research and Treatment Program is led by Doctors Cynthia Chin, MD, William Dillon, MD, Christopher Hess, MD, PhD, and Sharmila Majumdar, PhD. This program focuses on research to advance the practical utility of CT and MR imaging of the spine and peripheral nerves.

The UCSF Spine Neuroradiology team is continuously exploring the use of advanced imaging tools to better diagnose and treat spinal cord and peripheral nerve disorders and to better diagnose these disorders and assess their clinical implications.

Another focus of the group is the use of MR in the evaluation and treatment of patients with peripheral nerve disorders.

More information is available about treatment at The UCSF Precision Spine and Peripheral Nerve Center.

Physicians are welcome to contact us to discuss patients or request more information; please email Dr. William Dillon at [email protected] or Dr. Cynthia Chin, MD at [email protected].