Leading the Way in MRI

Leading the Way in MRI
HMRI’s quest for better ways to detect small
brain tumors, and to improve diagnostic images
of other tumors and of the brain itself, led to our
early interest in the prospects for using magnetic
resonance in medicine. We established the first
clinical Magnetic Resonance Imaging center in
Southern California, which was only the fourth
in the United States. When we began, MRI was
still experimental. We recruited Dr. William G.
Bradley to head our MR program. We performed
free MRI exams on hundreds of patients who had
been referred for routine x-ray CT scans, and then
rigorously compared the results, leading to good
understanding of the advantages of MRI in various
maladies. New knowledge we developed was a
major factor in approval of MRI for regular clinical
use by the U.S. Food and Drug Administration,
and in approval by Medicare and private insurers
of payment for the procedure.
As part of the MRI program, we established
one of the first and best fellowship programs for
radiologists who wanted to learn MRI, turning out
leaders who went on to run programs throughout
Hetero-nuclear MR
Virtually all routine MR exams are done by using
magnets and radios that are tuned to the resonant
frequency of hydrogen ions, or protons. These are
abundant and collectively give off relatively strong
signals, leading to good diagnostic pictures and
well-defined spectra. However, there are other
atoms that can reveal other valuable diagnostic
Southern California, around the United States, and
in other parts of the world. Another result of the
program was publication of several MRI textbooks,
including one that went through several editions.
In addition, early MRI radiologists who needed
expert “over-reading” in difficult cases were able
to consult with HMRI through our teleradiology
system, which enabled fast exchange of highresolution sets of MR images for discussion. Teleradiology is now a mainstay of medicine.
MR Spectroscopy
MRI, CT and many other medical imaging methods show internal details of body anatomy. HMRI
recruited Dr. Brian Ross from England to develop
MR spectroscopy as a diagnostic tool. Spectroscopy
uses the same basic equipment as many anatomical
imaging MR scanners, but
adds special accessories to
allow chemical analysis of
metabolic activity in the
brain, heart, tumors and
other parts of the body.
One of the first and most
here, the Proton Brain Exam (PROBE), introduced
metabolic markers that give neurologists a new
tool for determining whether or not a patient is
truly in a persistent vegetative state. An example
information, and HMRI has had an important role
in developing their use. One is carbon, which when
labeled can be used to follow details of metabolism
not traceable with proton MR spectroscopy. Another
is nitrogen, which can be used to follow amino acid
and protein changes. Applications include better
diagnosis of neurological diseases.
is near drowning victims, typically children who
have been rescued from water and undergone
successful CPR to restore their heartbeat, but still
show no sign that their brain
functions are intact. With the
PROBE exam, doctors can determine whether or not all or
most brain cells are still alive.
Knowing that they are saves
lives by leading to extended
life support until the patient
awakens, neurologically intact.
Another use of MR spectroscopy is to follow glutamate
in the brain. Here Drs. Ross and Keiko Kanamori
have conducted a long series of studies on how
this compound changes in patients with epilepsy.
When Huntington Hospital
wanted to launch its internal
medicine residency program,
it proposed the recruitment of
Dr. Richard Bing from Detroit
to head it. The Hospital called
on HMRI to accommodate
his laboratory research so he
could continue path-breaking research on cardiac
metabolism, vascular physiology and pharmacology,
and use of radioactive tracers in diagnosis.
With a stellar background at the Carlsberg and
Rockefeller Institutes, and at Johns Hopkins, Dr.
Bing became widely recognized for studies on how
alcohol affects heart muscle metabolism, how drugs
including calcium channel blockers work, how the
cells lining arteries modulate contraction of the
smooth muscles in their walls, and how COX-2
inhibitors like Vioxx can pose an unacceptable risk
in some patients. His studies using the intra-vital
microscope, that moved to keep tiny arterioles in
focus during pulsation, revealed fine details of
micro-circulation through high-speed photography.
The lab became a center for young cardiologists
finishing their residencies in the US, in Europe, and
around the world. It was said by many of them that
a year’s research fellowship here not only gave them
their “BTA” (Been To America), but was indispensible for launching their own careers in research,
whether in university hospitals, the pharmaceutical
industry or in research institutes.
Build on strengths
HMRI opened in 1952 to create research opportunities to attract and retain physicians dedicated
to improving the current medicine available. Since
its inception, our outstanding biomedical and
clinical researchers have transformed healthcare
and enriched the lives of countless individuals. As
we celebrate our first 60 years, we look forward to
a future built on a strong foundation of scientific
discovery connecting the brightest research minds
in the country to the practice of medicine.
734 Fairmount Avenue
Pasadena, CA 91105-3104
(626) 397-5804
Six Decades of Biomedical
Discoveries and Development
Neurosurgery Research
of the American Medical
Association, and became
prototype safety
car based on this
research incorporated many of the
safety features recommended in the article: raised headrests, strengthened seats, secure door locks, recessed knobs on the
dash, and seat belts. The result: increased emphasis
on auto safety and hundreds of thousands of lives
saved and severe injuries prevented.
The Hydrocephalus Shunt
“Water-on-the-brain” in children was once virtually untreatable. Drs. Robert Pudenz and William
Agnew, working in our labs, established that new
formulations of silicone rubber could be made toler-
Cancer Cell Biology
The advent of computed tomography (CT) x-ray
scanners brought the first wave of revolutionary
changes to diagnostic imaging of the brain. A
challenge was to use the resulting new sensitivity and precision to directly guide neurosurgery.
HMRI neurosurgeons and engineers, working with
Caltech computer scientists, developed a CT and
computer-guided brain surgery system that included
a minimally invasive binocular brain endoscope,
along with a 3-dimensional display system to help
guide surgery. The result: less collateral damage
when removing small brain tumors, some about the
size of a pea.
Early-on, it became apparent to clinicians and laboratory
scientists alike that understanding the biology and chemistry
of living cells would hold the
key to better prevention and
treatment of cancer. This led to
establishment by Drs. Charles
M. Pomerat and Donald E.
Rounds of one of the country’s
leading tissue culture laboratories, where human cells could be grown in life-like
laboratory conditions for experimentation. Studies
of smog established that some of its components
can lead to lung cancer, and showed how chromosomes become damaged and lead to the abnormal
cell division typical of malignancy. Other studies assessed the susceptibility of cancer cells to potential
Electrical Stimulation
Pioneering Work in Auto Safety
Some of HMRI’s deepest roots are in neurosurgery.
Drs. Hunter Shelden and Robert Pudenz served
together as medical officers heading projects at
the U.S. Navy Medical Center Institute of Medical
Research in Bethesda, Maryland during World War II.
Their studies of traumatic head injuries led to further
studies here when they returned to Pasadena.
One early project was to have engineers and
technicians take apart automobiles from accidents
resulting in serious injury or death. The resulting
analysis led them to suggest for the first time many
of the safety features now common in our cars. The
work was published as a lead article in the Journal
CT-Guided Brain Surgery
able when implanted permanently in patients, and
that these materials could be shaped into tubes with
valves. This device drained excess fluid from inside
the brain into the chest or abdomen, allowing the
brain to develop normally instead of expanding
the developing skull, or being compressed within
it. The result: tens of thousands of childhoods and
lives saved to develop normally.
Today, in addition to pediatric hydrocephalus,
this shunt technology is used to treat some kinds of
dementia in older patients whose brains become
“waterlogged.” Also, such shunts play a vital role
saving lives after trauma or cerebral hemorrhage,
when pressure must be relieved in emergencies.
HMRI scientists have played a pivotal role in
developing electrical stimulation devices, similar in
some ways to cardiac pacemakers, but connected to
nerves or to the brain itself. The challenge has been
to develop electrodes and signaling patterns that
are both safe and effective when used for long periods. Building partly on technology developed here
for the hydrocephalus shunt, HMRI neuroscientists
and engineers developed the most successful nerve
electrodes ever designed, which have been incorporated into neural stimulation systems. Example:
epilepsy, where some types of seizures can be prevented or stopped early by vagal nerve stimulation
(VNS). Thousands of patients treated this way have
been able to return to full and productive lives.
Cancer Research
Our earliest cancer research developed new ways
to precede or follow cancer surgery with radiation
or chemotherapy, keeping track of outcomes with
the area’s first tumor registry, sponsored in part
by the National Cancer Institute. Radiotherapy included pioneering therapy with implanted radioactive “seeds,” as well as high-voltage external beam
therapy, including the area’s first “cobalt-bomb.”
Innovations in chemotherapy included administration prior to surgery to shrink tumor margins and
allow more effective surgery. Other innovations included isolated perfusion of powerful drugs, so they
circulated only through the blood supply coursing in
and around tumors, while reducing damage to the
rest of the body.
Our affiliated Pasadena Tumor Institute, led by Dr.
George Sharp, and our laboratory researchers led
southern California in multi-specialty teamwork devoted to cancer, bringing surgeons, radiotherapists,
medical oncologists and pathologists together with
chemists and physiologists to
analyze new cases and plan
therapy together. Team members served as key faculty members on the cancer services at
Los Angeles County General
Hospital, at USC and at Loma
Linda University.
new anti-cancer drugs, and to radiation.
One of the ongoing legacies of this
program is the PC-3 prostate cancer cell
line, now used worldwide. It originated
as a metastasis in the bone of a patient
of urologist Dr. Lawrence W.
Jones, who helped organize
our prostate cancer program. In the lab, he worked
with Drs. Edward Kaighn,
Yasushi Ohnuki and Shankar
Narayan to preserve and
document PC-3 as an unparalleled high fidelity
laboratory model of cancer in the body. An outgrowth of this work is insight into how the slow
but inexorable spread of some such cancers can
be blocked with new strategies, like blocking their
energy metabolism instead of their cell division.
First Medical Use of Lasers
The high reputation of our cancer physicians
and researchers led Hughes Research Laboratories
to present their second prototype pulsed ruby laser
to us for research. Studies included experimental
treatment of disseminated melanoma, which was
the first time a laser was ever used in medicine.
Drs. Donald E. Rounds and James T. Helsper built
on this initial experience both with high-powered
lasers for surgery and with an emerging range of
gas lasers emitting beams ranging across the color
spectrum, each with exciting applications, many
of which were pioneered here. One was the first
intracellular nano-surgery.
Another was advanced
work for the U.S. military
defining damage thresholds for laser beams, now
incorporated into the
design of vital protective
gear. Work here led to
the formation of the
Beckman Laser Institute
and Medical Clinic at
UC Irvine.
Surgery, radiation and chemotherapy are
sometimes inadequate to control cancer. Biological therapy, that is supercharging the body’s own
natural defense systems against cancer, offers promise
therapies, and in some
cases, for making
gentle, yet still effective. Drs. Marylou Ingram,
Skip Jacques and Donald Freshwater pioneered
immunotherapy of malignant brain tumors by
collecting lymphocytes, which are natural immune
cells, from patients, expanding their numbers and
tumor-killing potential in our tissue culture lab,
and then implanting them back into the sites of
brain tumors in patients. Results in more than 200
patients were encouraging and stimulated ongoing efforts to make biotherapeutics an effective
21st century weapon against cancer.