working with the Biograph mMR, Siemens Healthcare’s molecular MR
technology with simultaneous image acquisition, have identified several
disease areas in which PET/MR may increase diagnostic and therapeutic
capabilities. Their findings are paving the way for new PET/MR protocols
that will help enhance routine applications and lift medicine to a
higher level of personalized care.
An engineering marvel
mMR uniquely allows a combined approach to imaging not only anatomical
and functional characteristics of disease, but also their biochemical
characteristics. Prior to the advent of this system, integrating PET and
MR technologies was considered nearly impossible because of the
functional incompatibility of the photomultiplier tubes housed in PET
detectors with the strong magnetic field generated by the MR.
key technology enabler was the development of detectors for positron
annihilation capable of functioning inside the strong magnetic field of a
clinical MR scanner. The scintillation crystal blocks in conventional
PET that read out by photomultiplier tubes (PMT) are susceptible to
magnetic fields and had to be replaced for integration with MR. The
solution was the introduction of the new detector solution based on
avalanche photo diodes (APD) in combination with lutetium
oxyorthosilicate (LSO) crystals, which is suitable for use in strong
magnetic fields. It is a key enabler for the simultaneous acquisition of
PET and MR, as well as offering high PET performance. Another advantage
of APD detectors is that they are smaller and lighter, thus enabling
room to integrate into a whole-body 3-tesla MR with an adequate bore
Commercially available in Europe and in the U.S., the Biograph mMR is already in use at installations around the world.
New clinical opportunities
The Biograph mMR may be an engineering marvel, but what does it mean for patient care?
at luminary sites are making headway on the Biograph mMR, developing
novel approaches to the understanding, diagnosis, and treatment of
“The PET/MR enables us for the first time to combine
morphology, function, and metabolic activity in one measurement,” said
Markus Lentschig, MD, Center for Modern Diagnostics (CEMODI), Bremen,
Germany. “PET has molecular sensitivity, and MR lets us image anatomic
details with very high spatial and high temporal resolution with
excellent soft-tissue contrast. Now we can examine morphology and
metabolic activity with one scanner. On the MR side, we can examine
functional parameters and employ the BOLD (blood-oxygen-level
dependence) technique in the brain, and we have tools for spectroscopy
and diffusion-weighted imaging.”
Advances in oncology
on initial findings, physicians foresee the first routine applications
in tumor delineation and characterization. PET/MR’s ability to detect
small lesions in soft-tissue is promising for diagnosis and treatment of
a wide range of cancers, including those of the head and neck, the
liver, lung, and prostate, as well as endometrial, ovarian, and cervical
“PET/MR is effective due to high soft-tissue contrast
and the additional metabolic information, especially for primary tumor
and local tumor recurrence, for example, in the liver. Overall,
malignancies in the pelvic region will be a possible future application
for PET/MR,” indicated Nina Schwenzer, MD, Management PET/MR Center,
Department of Diagnostic and Interventional Radiology, Tuebingen, and
Holger Schmidt, PhD, Managing Physicist, PET/MR, Department of
Diagnostic and Interventional Radiology, Tuebingen Germany.
advantage of using MR over CT for tumor detection in the liver is
notable because MR is a more specific test for characterizing liver
pathology than CT, said Bruce R. Rosen, MD, PhD, Professor of Radiology,
Harvard Medical School, and Director of the Martinos Center for
Biomedical Imaging, Massachusetts General Hospital (MGH), Boston, MA.
to individual modalities, PET/MR may pick up additional lesions in
patients with extensive metastatic spread. “In patients with metastatic
spread, the high sensitivity of diffusion-weighted imaging combined with
PET may help identify additional lesions,” said Dr. Schwenzer.
prostate cancer, Dr. Lentschig has found that PET/MR assists with
binary diagnosis for prostate-specific antigen (PSA) recurrence of the
tumor. He anticipates it will also enhance detection of metastases in
the liver, lymph nodes, and bone, as well as those in the brain and head
In patients with multiple myeloma and lymphoma, “there
is the benefit of the added contrast and the bone marrow where some
patients with multiple myeloma all have bone marrow involvement where CT
is not as good as MRI in discriminating,” said Alexander R. Guimaraes,
MD, PhD, Medical Director of the Martinos Center for Biomedical Imaging,
Massachusetts General Hospital, Boston, MA.
Simultaneous acquisition provides spacial accuracy
are several advantages to the simultaneous data acquisition enabled by
Biograph mMR, including temporal correlation of PET and MR imaging data,
reduced imaging time compared to sequential imaging, and cardiac and
respiratory motion correction of PET data.
Of these advances,
MR-based motion correction for PET is especially useful for reducing the
effects of misregistration caused by patient movement and physiological
processes when imaging the lung, the upper abdominal region, and heart.
In the Biograph mMR, tissue attenuation is obtained in an image
segmentation-based approach. Depending on the sequence type used, air,
lung, fat, muscle, and bones are segmented and provided according to PET
correction values. In the head and neck region, attenuation correction
is achieved with an ultrashort echo-time (UTE) sequence, which also
provides segmentation of the bone. All other body parts are
attenuation-corrected by a Dixon technique providing 2 images where
water and fat are ‘in phase’ and in ‘opposed phase.’ This allows for
reconstruction of fat-only, water-only and fat-water images, resulting
in tissue segmentation of air, fat, muscle, and lungs.
“We use the
MR-based motion correction for PET data, with ECG-triggering for
cardiac exams, and with the navigator-echo technique with the MR for
abdominal imaging, in particular for the liver and pancreas,” said Dr.
Lentschig. “We have used navigator-echo techniques (2D-PACE), and now
use them for PET, too.”
At MGH, doctors are using real-time motion
correction with MR to directly impact the reconstruction of the PET
data. “It shows specific sensitivity to small lesions, especially
metastatic lesions within the liver,” said Dr. Rosen.
Schwenzer and Dr. Schmidt believe MR-based motion correction could
result in higher detection rates for small lung and upper abdominal
lesions in PET images.
Simultaneous acquisition of PET and MR
images also provides the accuracy needed to differentiate radiation
change or post-surgical change from residual tumors, indicated Pamela K.
Woodard, MD, Professor, Radiology, Head, Advanced Cardiac Imaging
(Cardiac CT/MRI), Division of Diagnostic Radiology, Cardiothoracic
Imaging Section, Mallinckrodt Institute of Radiology, Washington
University in St. Louis, MO. “In pelvic imaging, for instance, a lot of
patients get PET or MR imaging as opposed to CT. In this case you have
the simultaneous acquisition without the need to use the CT for
attenuation correction,” said Dr. Woodard.
The combination of MR
and PET adds perfusion information to dynamic PET data. These techniques
might play an important role for therapy adoption and when working with
specific PET tracers. The advantage of the additional perfusion
information is twofold: On one hand, it will be relevant in monitoring
anti-angiogenic strategies. On the other, dynamic-contrast imaging plays
an important role in tumor characterization and lesion detection. “This
could be especially useful for developing new PET tracers or MR
contrast media,” said Dr. Schmidt.
The development of new PET and MR tracers brings doctors a step closer to delivering personalized medicine.
next level PET/MR lends itself to is targeted-receptor oncologic
imaging,” said Dr. Woodard. Physicians at Washington University plan to
investigate receptors expressed by different tumor types to determine if
certain receptors are present even without biopsy and whether a certain
tumor is receptive to a specific therapeutic agent.
mission is to move toward a more personalized treatment of that tumor.
We think we can develop a better biopsy by using these combined
structural assessments, which you can get with PET and MR in a
simultaneous acquisition. We can get a better assessment of the overall
tumor behavior with PET/MR than from pathology alone,” said Robert C.
McKinstry, III, MD, PhD, Radiologist-in-Chief, St. Louis Children’s
Hospital, Professor of Radiology and Pediatrics, and Director, Center
for Clinical Imaging Research, Mallinckrodt Institute of Radiology,
Washington University in St. Louis.
Reduced radiation improves patient care
important consideration in any imaging exam is exposure to radiation.
Since only the PET component requires exposure to ionizing radiation,
PET/MR significantly lowers dose exposure to patients compared to other
imaging modalities with radiation.
This is particularly
relevant in the pediatric* population, young adults, women of
child-bearing age and, as Dr. Rosen noted, “in patients we call the
frequent flyers—patients with lymphoma who have repeated exams over an
extended period of time.”
New insights in neurodegenerative disease
of the most anticipated advances PET/MR is expected to impact are in
neurodegenerative disorders, such as Alzheimer’s, other dementias, and
Recent data suggest that PET together with
quantitative morphometry of MR may have the ability to discriminate mild
cognitive impairment from a normal control,” he said. “I really think
the combination of PET/MR is going to be the most specific early test we
can give for patients who will undergo a rapid course of cognitive
decline. Also under way is the use of special techniques that combine
metabolic information from PET with BOLD, fiber-tracking, and
diffusion-weighted imaging. “The BOLD experiment is going to be very
important. We are developing a delivery method for getting short
half-life radiopharmaceuticals into the scanner room to look at PET
measurements of blood flow, blood volume, and oxygen metabolism, and
oxygen extraction,” said Dr. McKinstry, who expects PET/MR to open new
opportunities in hemorrhagic stroke and stroke rehabilitation.
Dr. Schwenzer and Dr. Schmidt are focusing on the detection of varying
patterns in radiopharmaceutical uptake and anatomical changes in MR
images. They added, “In the future, we are also interested in
researching functional MRI in correlation with new PET tracers.”
Cardiac imaging: One-stop shop
cardiac stress exams, simultaneous acquisition of cardiac MR and PET is
somewhat like a one-stop shop. Dr. Woodard is preparing to conduct PET
ammonia stress perfusion imaging, along with simultaneous cardiac MRI.
She also thinks the system may be useful in assessing viability and
providing direction to certain electrophysiology/cardiology procedures.
new radiopharmaceuticals on the horizon, there lies tremendous
potential for cardiac PET/MR imaging. For example, Dr. Woodard hopes to
assess a PET perfusion agent, flurpiridaz 18F (currently in clinical
trials), for patients with known or suspected coronary artery disease,
as well as other novel agents for atherosclerotic plaque assessment.
have developed a radiopharmaceutical that is targeted to receptors
present in atherosclerosis. These receptors appear to be overexpressed
in plaque that is less stable. It is being evaluated whether PET/MR and
this radiopharmaceutical could identify plaque more likely to rupture
and cause a stroke. This would be done by looking simultaneously at the
anatomic features of the plaque with MR and the potential of the uptake
of the radiopharmaceutical with the PET,” said Dr. Woodard. “With PET
you’re looking at functional information, and then with MR you’re
looking at the anatomy—the plaque thickness and the lipid core.”
emerging applications in development at MGH involve detailed
visualization of contractile function in patients with diastolic
dysfunction acquired on MR combined with the ability to quantify
perfusion with PET.
with any emerging technology are changes to the way procedures are
conducted. PET/MR, in the clinical setting, requires adjustments to
workflow, affecting exam time; technical training; and a new approach to
There are pros and cons to patient
throughput with PET/MR. Compared to PET-CT exams, PET/MR tests take
longer. The total time depends on the MR protocols. After a whole-body
exam, the MR protocol must be optimized to answer the clinical question.
This may involve exams with very high spatial resolution, contrast
studies, dynamic studies, spectroscopy, diffusion-weighted imaging, or
functional MRI. The total scan time for a whole-body examination very
much depends on the selected MR protocols that run simultaneously with
the PET. In a minimum protocol, the acquisition can be as short as 20
min for a whole-body scan. However, users typically add more MR
sequences in routine protocols to strengthen diagnostic confidence and
make full use of the MR portion of the machine. “We have optimized our
MR, and now a whole-body exam takes 60 min. For specific questions like
prostate cancer, the high spatial resolution prostate exam, including
spectroscopy, requires an additional 20 minutes,” said Dr. Lentschig.
Dr. Guimaraes likens the learning curve for PET/MR to the initial
stages of PET-CT adoption, he sees distinct advantages in PET/MR
“Since PET requires 10 or 15 minutes and because of the
simultaneous nature of the system, one of the benefits is you can run
MRI sequences both for attenuation correction and for anatomic
localization and soft-tissue contrast. You are acquiring the MRI
information simultaneously with the PET information, so you are not
wasting any time in any of those table positions,” said Dr. Guimaraes.
“You also save patients from waiting for another exam, you have the
fused information simultaneously, and lastly, you have the benefit of
motion-tracking information to isolate and improve your spatial
confidence of the radiopharmaceutical avidity of liver lesions, which
are normally moving with patient respiration.”
As part of the
learning curve, imaging technologists will need training in both MR and
PET exam planning and in handling radioactive tracers.
physicians, reading studies will involve a larger amount of image data.
“Similar to diagnostic PET/CT exams with contrast, the images should be
read by a nuclear medicine physician and a radiologist,” said Dr.
PET/MR’s outlook gets personal
expect to make inroads in several other important areas using
simultaneous PET/MR. “My hope is to be able to use PET/MR for breast
cancer with dedicated breast coils, but we need a special breast coil to
combine PET and MR for examining the breast,” said Dr. Lentschig.
potential use for PET/MR is as an alternative to CT for radiotherapy
planning, said Dr. Lentschig. Researchers at University Hospital in
Tuebingen have already launched several clinical trials, designing
radiation treatment plans based on PET/MR data.
“The first step
will be the implementation of multiparametric imaging in PET/MR
protocols in the framework of prospective studies,” indicated Drs.
Schwenzer and Schmidt. “Then the relevant parameters can be transferred
into the clinical routine.”
By enabling users to generate the
location, function, and metabolic activity of organs in a single fused
image, Biograph mMR is providing new opportunities for imaging.
PET/MR may be the modality that ushers in a new era for personalized
medicine. “If we see the next 20 years as the rise of individualized
medicine and molecular medicine, I think the PET/MR is the first
diagnostic tool of that next generation,” said Dr. Rosen. “It really
should be the diagnostic tool for personalized molecular medicine.”
*MR scanning has not been established as safe for imaging fetuses and
infants under 2 years of age. The responsible physician has to decide
about the benefit of the MRI examination in comparison to other imaging