National Institute of Biomedical Imaging and Bioengineering
Painless Imaging Reduces Need for
Although doctors rely on needle biopsies of bone marrow to diagnose and oversee treatment of leukemia, the
procedures have limited value because they sample only the area where the needle is inserted. The core sample
that is removed may not provide a true indication of the body’s overall health.
Now, a combination of advanced imaging techniques may offer patients and doctors alike a noninvasive
alternative to traditional biopsies and a method for monitoring patient response to therapeutic treatments. The
modified magnetic resonance imaging (MRI) technique can assess a patient in less than 20 minutes and does
not require injecting the patient with specialized dyes known as contrast agents. The new technique was
developed by researchers at Cornell University’s Weill Medical College and Memorial Sloan-Kettering Cancer
Center in New York.
“In April 1998, we did an MRI scan of a single
patient, a very sick man with acute myelogenous
leukemia, expecting to measure small differences in
image contrast between normal and leukemic
marrow,” says Douglas Ballon, a physicist and
Director of Weill Medical College’s Citigroup
Biomedical Imaging Center. But surprisingly, the
image the team saw on the monitor was stark even
without the use of contrast agents. The diseased
marrow stood out, bright against the darker
surrounding bone. “We were expecting to measure a
very subtle effect, and instead found a method for
imaging leukemic marrow over large areas of the
body where very little signal was present from other
structures,” he says. “Once we realized that we could
do this, we began to think about true whole-body
Essentially, the strong bright areas in Ballon’s scans
of leukemic marrow show water inside cells. On most
MRI scans the image intensity reflects a combination
of intracellular and extracellular water. With the
Cornell imaging technique, MRI scans reveal the In this magnetic resonance image from a 20-year-old patient
presence of leukemia by distinguishing between with acute lymphocytic leukemia what appear to be images of
intracellular water (water inside cells) and bone are actually signals from the bone marrow that are
thought to arise primarily from leukemic blast cells. The new
extracellular water. Inside the body, extracellular MRI technique may provide a less invasive way to identify and
water is present in the plasma part of blood and other track cancer.
fluids. By tweaking the software that processes the Image courtesy of Dr. Douglas Ballon, Weill Cornell Medical
signals from the scans, the Cornell/Sloan-Kettering College.
team has created a tool that highlights dense
concentrations of cells and suppresses signals from fat, muscles, bladder contents, and other tissues.
The new MRI technique may help doctors monitor treatment of leukemia and several other diseases as well.
“We believe it will also help in lymphoma, metastatic breast cancer, and prostate cancer,” Ballon says. For
these cancers, the ability to assess the whole-body burden of disease in a patient may help doctors and patients
to decide how aggressive future therapy should be.
Toward Better Biopsies
Leukemia is a disease in which the bone marrow makes too many white blood cells.
Normally, the body produces bone marrow stem cells that develop into mature blood cells. The three types of
mature blood cells are red blood cells, which carry oxygen, white blood cells, which fight infection, and
platelets, which help to prevent excessive bleeding by forming blood clots. In chronic myelogenous leukemia,
the body directs too many bone marrow stem cells to become granulocytes, a type of white blood cell. Some of
these bone marrow stem cells never mature into white blood cells. Gradually, the granulocytes and immature
cells, known as blast cells, crowd out the red blood cells and platelets in the bone marrow.
Ballon’s research is a collaborative venture. His expertise is in the physics of MRI – how protons in human
bodies react under the scanner’s strong magnetic field, and how to interpret the signals they produce. He works
with Dr. Ann Jakubowski, a hematologist who treats leukemia patients, and a team of other specialists in
medical physics and prostate cancer.
The team has studied some 70 patients and about a dozen healthy volunteers so far. About half of the patients
had leukemia or lymphoma, and half had metastatic prostate cancer. Metastatic cancers – those spreading
throughout the body – are of special interest because they are hard to track. Doing needle biopsies everywhere
to look for tumors is impractical, and tumors often do not show up well on X-rays, CT scans, or other images.
“Because of certain properties of the water within the tumor cells they show up well on these scans, even when
they are inside bones,” Ballon says. Being able to see tumors or leukemic marrow in whole-body scans is not a
screening tool, he says. “MRI scans are too expensive for screening for most types of cancer. What we do
think it will be used for is monitoring treatment,” he says.
The team has taken scans before and after treatment for both leukemia and prostate cancer patients. “Scans
taken a day or two after chemotherapy have shown striking differences,” Ballon says. In leukemia patients,
marrow in the pelvic bones that appeared bright on the images because of the high concentration of blast cells
became a normal pale gray. Similarly, the appearance of prostate tumors “faded” after chemotherapy. “This is
the promise of the technique,” Ballon says. “When patients are given chemotherapy, we hope to be able to
check within a few days to see how effective it is, with no discomfort to the patients.”
The Cornell/Sloan-Kettering team uses a typical MRI scanner found in many hospitals, so the new technique
could easily be adopted elsewhere. Meanwhile, Ballon and his colleagues are refining the new approach. “We
will achieve better resolution (the ability to spot smaller tumors) soon, and be able to image difficult areas
such as the chest by using better hardware now available with the scanner.”
Research on the new technique has been supported by the National Institute of Biomedical Imaging and
Bioengineering and the National Heart, Lung, and Blood Institute.
Ballon D, Watts R, Dyke JP, Lis E, Morris MJ, Scher HI, Ulug AM, Jakubowski AA. Imaging therapeutic response in
human bone marrow using rapid whole-body MRI. Magnetic Resonance in Medicine 52:1234-1238, 2004.