Marcos Duarte Guimaraes1, Alice Schuch2, Bruno Hochhegger3, Jefferson Luiz Gross4, Rubens Chojniak5, Edson Marchiori6. 1. MSc and PhD Fellow, MD, Radiologist, Specialist in Chest and Oncological Imaging, Hospital Heliópolis and A.C.Camargo Cancer Center, São Paulo, SP, Brazil. 2. MD, Radiologist, Full Member of Colégio Brasileiro de Radiologia e Diagnóstico por Imagem (CBR), Specialist in Oncological Imaging, MD, Hospital Moinhos de Vento, Porto Alegre, RS, Brazil. 3. Post-PhD, MD, Associate Professor, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil. 4. PhD, MD, Oncological Surgeon, Head of Thoracic Surgery Department, A.C.Camargo Cancer Center, São Paulo, SP, Brazil. 5. PhD, Head of Imaging Department, A.C.Camargo Cancer Center, São Paulo, SP. Brazil. 6. PhD, Full Professor, Universidade Federal Fluminense (UFF), Niterói, RJ, Associate Professor, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
Abstract
In the investigation of tumors with conventional magnetic resonance imaging, both quantitative characteristics, such as size, edema, necrosis, and presence of metastases, and qualitative characteristics, such as contrast enhancement degree, are taken into consideration. However, changes in cell metabolism and tissue physiology which precede morphological changes cannot be detected by the conventional technique. The development of new magnetic resonance imaging techniques has enabled the functional assessment of the structures in order to obtain information on the different physiological processes of the tumor microenvironment, such as oxygenation levels, cellularity and vascularity. The detailed morphological study in association with the new functional imaging techniques allows for an appropriate approach to cancer patients, including the phases of diagnosis, staging, response evaluation and follow-up, with a positive impact on their quality of life and survival rate.
In the investigation of tumors with conventional magnetic resonance imaging, both quantitative characteristics, such as size, edema, necrosis, and presence of metastases, and qualitative characteristics, such as contrast enhancement degree, are taken into consideration. However, changes in cell metabolism and tissue physiology which precede morphological changes cannot be detected by the conventional technique. The development of new magnetic resonance imaging techniques has enabled the functional assessment of the structures in order to obtain information on the different physiological processes of the tumor microenvironment, such as oxygenation levels, cellularity and vascularity. The detailed morphological study in association with the new functional imaging techniques allows for an appropriate approach to cancerpatients, including the phases of diagnosis, staging, response evaluation and follow-up, with a positive impact on their quality of life and survival rate.
Entities:
Keywords:
Cancer imaging; Diffusion; Functional imaging; Magnetic resonance imaging; Neoplasia; Oncology
Ever since Wilhelm Conrad Röntgen discovered x-rays in 1895 in Germany, the field
of imaging has been undergoing development and expanding its application in
medicine(. In the field of
oncology, imaging has been playing a fundamental role, providing valuable data for a
better management of cancerpatients. Imaging methods may be utilized in different
phases, from screening up to post-therapeutic follow-up(. Radiography,
ultrasonography and computed tomography are most frequently utilized and, many times,
are the only available methods for the evaluation of cancerpatients. Such tools are
primarily based upon anatomical abnormalities and, when available, on the pattern of
post-contrast enhancement of affected structures(. However, with advances in the technology and therapy, an
exclusively morphological evaluation may be insufficient for appropriate therapeutic
decision making. An example of such advances is the application of the "Response
Evaluation Criteria In Solid Tumors" (RECIST) whose main focus is the evaluation of the
largest diameter of the lesion. Several studies have demonstrated the limitations of
such criteria in predicting the biological behavior and therapeutic success. The new
oncologic therapies have created a paradigm in the evaluation of cancerpatients. The
functional criteria became more faithful in depicting the diseases' activity and
biological response to treatment, differently from the traditional morphological
criteria(.Currently, magnetic resonance imaging (MRI) is an imaging diagnosis method that is well
established in the clinical practice, but it is in continuous development(. For more than 30 years this method has
presented significant progress in different fields of medicine, particularly in cancerpatients, including different steps of oncologic management, such as detection,
characterization, staging, response evaluation and post-therapeutic follow-up(. MRI can produce three-dimensional
images in a noninvasive way, without the risks of ionizing radiation and with excellent
spatial and contrast resolution, allowing for a very accurate tumor evaluation. The
innovation is focused principally on improving the anatomical resolution and, more
recently, on the advent of functional and molecular methods. Such advances have improved
the application of MRI in the evaluation and management of oncologic patients(.MRI can provide morphological data, such as size, contours, number of lesions, presence
of edema and necrosis, relationship with adjacent structures and characteristics related
to intravenous contrast enhancement(. However, physiological and molecular metabolism alterations which
normally precede morphological alterations are not usually recognized by traditional
morphological techniques. The introduction of novel MRI techniques allowed the
evaluation of structures and different physiological processes of the tumor
microenvironment(. Combined analysis of anatomical and
functional findings allows a more comprehensive evaluation of the extension and activity
of neoplastic disease. The appropriate evaluation of the oncologic status allows for the
establishment of better therapeutic strategies, with a favorable impact on the prognosis
and survival(. Angiogenesis, cell metabolism and cellularity can be
evaluated by perfusion, spectroscopy and diffusion, respectively. Theses techniques are
examples of functional methods provided by MRI.The present review article is focused on some of the main recent advances of functional
MRI and their impact on the management of oncologic patients.
DIFFUSION
The principle of diffusion-weighted MRI is related to the random motion, also known as
"Brownian" motion of water molecules protons throughout the biological tissues. Such
motion causes phase dispersion of the spins, resulting in signal loss on
diffusion-dispersion sequences. However, in the human body there are natural biological
barriers to this motion due to the interaction between cell membranes and macromolecules
(Figure 1). Diffusion-weighted imaging (DWI)
allows for the qualitative analysis of the water molecules diffusion in the tissues by
the interpretation of the signal intensity in the region object of the study. The
quantitative analysis can also be performed calculating the apparent diffusion
coefficient (ADC) attributing absolute values in mm2/s for the signal
intensity of the region object of study(.
Figure 1
Demonstration of water molecules motion in the intra and extracellular spaces and
within the extracellular space providing information on the degree of cellularity
of the tissues. On A, there are a greater number of cells restricting
the water molecules motion; on B, the cellularity is decreased, with
satisfactory molecular motion.
Demonstration of water molecules motion in the intra and extracellular spaces and
within the extracellular space providing information on the degree of cellularity
of the tissues. On A, there are a greater number of cells restricting
the water molecules motion; on B, the cellularity is decreased, with
satisfactory molecular motion.The technique is based upon the existence of barriers that restrict the water molecules
diffusion in their microenvironment, producing different contrast intensities in
different tissues. The motion of such molecules in the intracellular, extracellular and
intravascular spaces contributes to the balance of their distribution which reflects the
integrity of the barriers found in those structures. Cell membrane is the most known
barrier to diffusion of water molecules. Other examples of barriers are: structural
components, cell connections, tissue connections such as the cytoskeleton,
macromolecules, organelles and tight junctions. Thus different tissues will present
specific signal intensity and ADC according to their structural
characteristics(.The utilization of this technique has been described by different studies in the
literature, including the capacity to identify minimal ischemic tissue injuries in the
brain, many times preceding the morphological changes. DWI may also be utilized in the
evaluation of other types of brain lesions, including neoplastic (Figure 2), inflammatory, infectious and neurodegenerative
diseases(.
Figure 2
A 37-year-old female patient presenting with glioblastoma multiforme affecting the
right parietal lobe. On A, areas of hypersignal are observed at the
diffusion sequence (arrows), presenting correlation with areas of signal loss on
the ADC map (B), demonstrating restriction to water molecules motion
and increased cellularity. Courtesy of Dr. Leonardo Vedolin - Hospital Moinhos de
Vento, Porto Alegre, RS, Brazil.
A 37-year-old female patient presenting with glioblastoma multiforme affecting the
right parietal lobe. On A, areas of hypersignal are observed at the
diffusion sequence (arrows), presenting correlation with areas of signal loss on
the ADC map (B), demonstrating restriction to water molecules motion
and increased cellularity. Courtesy of Dr. Leonardo Vedolin - Hospital Moinhos de
Vento, Porto Alegre, RS, Brazil.The recent advances has also allowed the utilization of DWI in the evaluation of
extracranial organs(. The introduction of echo-planar imaging techniques,
multichannel coils and parallel MR imaging were decisive for the acquisition of
better-quality images, allowing DWI to be utilized in the study of other organs. During
the acquisition phase, the reduction of motion artifacts such as those related to
heartbeats, breathing and intestinal peristalsis, is aimed to improve the images quality
and the analysis of the findings(.Among the parameters applied in diffusion imaging, one of the most relevant is known as
"b value". Such a parameter is capable of adjusting the sensitivity level of this
sequence that is proportional to the duration and amplitude of the applied gradient and
the time interval between the gradients(. DWI is typically performed applying two b values at least (for
example, b = 0 or a low b, with values between 50 and 100, and a high b, with values
between 800 and 1000 s/mm2). On images with low b values, more "anatomical"
images are observed, with attenuation of the perfusion effects, i.e., with attenuation
of vessels and of the cerebrospinal fluid. However, on images with a high b value, the
tissues with increased cellularity are seen with increased signal intensity (Figure 3). In the case of tumor tissues, the water
motion is impaired by the presence of several barriers, maintaining the brightness of
the signal. However, tissues where cell disorganization is not present usually are
visualized with lower signal attenuation (Figure
4). The visual evaluation of signal attenuation at DWI is applied to detect and
characterize tumors, as well as to evaluate the treatment response in oncologic
patients(.
Figure 3
Diffusion-weighted images with different b values from a 47 year-old female
patient presenting with liver hemangioma in the transition between the V and VI
segments. The image with b value = 50 s/mm2 is more "anatomical", with
attenuation of the perfusion effects, i.e., attenuation of the vessels and spinal
fluid (A). On the images with higher b values (B,C) one observes, progressively,
attenuation of signal intensity in the healthy tissues, however the hemangioma
persists with high signal intensity (tissue with greater cellularity/ T2 effect).
Courtesy of Dr. Gustavo Luersen - Hospital Moinhos de Vento, Porto Alegre, RS,
Brazil.
Figure 4
Liver metastases in a 66-year-old female patient presenting with colon
adenocarcinoma, undergoing treatment with antiangiogenic drug bevacizumab.
Diffusion-weighted images with different b values: 200 s/mm2 (A) and
600 s/mm2 (B). The necrotic center of the metastatic lesions (green ROI
and white arrow) shows attenuation of signal intensity, with increasing b values
indicating less restriction to diffusion. In comparison, the peripheral zone of
the tumor (purple ROI) presents increased cellularity and little signal
attenuation with the increase of the b value.
Diffusion-weighted images with different b values from a 47 year-old female
patient presenting with liver hemangioma in the transition between the V and VI
segments. The image with b value = 50 s/mm2 is more "anatomical", with
attenuation of the perfusion effects, i.e., attenuation of the vessels and spinal
fluid (A). On the images with higher b values (B,C) one observes, progressively,
attenuation of signal intensity in the healthy tissues, however the hemangioma
persists with high signal intensity (tissue with greater cellularity/ T2 effect).
Courtesy of Dr. Gustavo Luersen - Hospital Moinhos de Vento, Porto Alegre, RS,
Brazil.Liver metastases in a 66-year-old female patient presenting with colon
adenocarcinoma, undergoing treatment with antiangiogenic drug bevacizumab.
Diffusion-weighted images with different b values: 200 s/mm2 (A) and
600 s/mm2 (B). The necrotic center of the metastatic lesions (green ROI
and white arrow) shows attenuation of signal intensity, with increasing b values
indicating less restriction to diffusion. In comparison, the peripheral zone of
the tumor (purple ROI) presents increased cellularity and little signal
attenuation with the increase of the b value.Applying different b values it is also possible to perform a quantitative analysis with
DWI. This particular analysis is usually performed on a workstation by calculating ADC
values (Figure 5). The ADC is independent from the
magnetic field intensity and can overcome the "T2 effects", thus allowing for a more
significant comparison of the results. The ADC is calculated for each image pixel and is
shown as a statistical parametric map. Areas with restriction to water molecules
diffusion demonstrate increase signal intensity at DWI and low values at the ADC
mapping: demonstrating the correspondence of both (Figure
6).
Figure 5
Quantitative analysis of DWI. A 70-year-old male patient presenting with
heterogeneous lesion in the hepatic segments VI/VII, with small satellite lesions.
On A, diffusion-weighted image (b = 600 s/mm2) demonstrating high
signal intensity in the peripheral zone of the dominant lesion (ROI 1 - purple),
low central signal (ROI 2 - purple) and high signal intensity in the satellite
lesions (ROI 3 - green). On B, ADC map demonstrates correspondence with DWI, with
low values in ROI 1 (1.3 × 10-3) and in ROI 3 (1.1 × 10-3)
and higher value in ROI 2 (1.7 × 10-3). The anatomopathological
analysis confirmed the tumor heterogeneity, a moderately differentiated
cholangiocarcinoma with areas of necrosis.
Figure 6
Dynamic MRI (DSC-MRI) of a high-grade neuroglial tumor (arrow) in a 16-year-old
patient. On A, axial post-gadolinium T1-weighted image showing two ROIs: 1
(purple) located in the tumor lesion, and 2 (green) located in the healthy tissue.
On B, the respective time-signal intensity curve demonstrates greater perfusion in
the tumor region in relation to the healthy tissue (> 2.0). On C, the rBV map
superimposed on the contrast-enhanced axial T1-weighted image demonstrates
increased perfusion in the tumor ROI (arrow).
Quantitative analysis of DWI. A 70-year-old male patient presenting with
heterogeneous lesion in the hepatic segments VI/VII, with small satellite lesions.
On A, diffusion-weighted image (b = 600 s/mm2) demonstrating high
signal intensity in the peripheral zone of the dominant lesion (ROI 1 - purple),
low central signal (ROI 2 - purple) and high signal intensity in the satellite
lesions (ROI 3 - green). On B, ADC map demonstrates correspondence with DWI, with
low values in ROI 1 (1.3 × 10-3) and in ROI 3 (1.1 × 10-3)
and higher value in ROI 2 (1.7 × 10-3). The anatomopathological
analysis confirmed the tumor heterogeneity, a moderately differentiated
cholangiocarcinoma with areas of necrosis.Dynamic MRI (DSC-MRI) of a high-grade neuroglial tumor (arrow) in a 16-year-old
patient. On A, axial post-gadolinium T1-weighted image showing two ROIs: 1
(purple) located in the tumor lesion, and 2 (green) located in the healthy tissue.
On B, the respective time-signal intensity curve demonstrates greater perfusion in
the tumor region in relation to the healthy tissue (> 2.0). On C, the rBV map
superimposed on the contrast-enhanced axial T1-weighted image demonstrates
increased perfusion in the tumor ROI (arrow).
PERFUSION
A great part of the molecular imaging techniques utilize exogenous markers that produce
the signal from the particle itself or from the pattern of contrast enhancement. For
example,, the marker may be a conventional intravenous contrast medium such as
gadolinium. The utilization of such agents has occurred with the advent of the dynamic
contrast enhanced (DCE) technique or perfusion MRI. In such techniques, the images are
sequentially acquired during the contrast agent passage through the tissue of interest,
allowing the characterization of lesions in different anatomical sites, including brain,
breast, gynecologic and prostate lesions. Such methods are not intrinsically molecular,
but allow for an indirect evaluation of molecular processes that affect the blood
flow(13). The quantitative and qualitative dynamic analyses of the MRI contrast
enhancement may also be useful in the differentiation of benign from malignant
musculoskeletal system tumors(.
Nowadays a very promising perfusion MRI technique without the utilization of
paramagnetic contrast is available. Such a technique, called arterial spin labeling, has
been utilized in the evaluation of the cerebral blood flow, but currently it is
available only in more advanced centers(.The conventional dynamic MRI technique is based on the concept of development of new
vessels (angiogenesis) associated with increased blood flow and vessels permeability,
which constitute essential conditions for metastatic dissemination of malignant
tumors(. The
microvascular structure of the tumor constitutes a relevant prognostic factor, and
perfusion MRI can provide information about this special characteristic in a noninvasive
way(. The images are often
acquired after infusion of low molecular weight gadolinium. The distribution of the
contrast medium in the intra- and extravascular regions will depend upon some factors
such as blood flow, vascular permeability and interstitial diffusion capacity. This
technique can be performed with T1-weighted gradient-echo (GRE-T1) and T2-weighted*
sequences(. The GRE-T1 sequences can more appropriately
characterize the alterations in vessels permeability and extravasation to the
extravascular space and are indicated for the evaluation of extracranial regions. The
T2-weighted* sequences are more frequently indicated for evaluation of the brain and
determine the blood flow volume and capillary tissue perfusion (Figure 6). With those sequences it is possible to perform
qualitative, semi-quantitative and quantitative measurements(. Qualitative
measurements can be obtained by means of signal intensity-time curves, often utilized in
the evaluation of breast carcinomas (Figure 7).
Semi-quantitative measurements are related to the differences in signal intensity before
and after contrast medium infusion (relative signal intensity). Quantitative
measurements are based on pharmacokinetic models which allow for data collection. Thus,
it is possible to create color parametric maps demonstrating the tumor behavior which is
important, for example, for the therapeutic planning( (Figure
6).
Figure 7
A 30-year-old female patient presenting with multicentric invasive ductal
carcinoma in the right breast and fibroadenoma in the left breast. On A, one
observes contrast-enhanced, dynamic 3D MIP image with subtraction, demonstrating
the presence of multiple breast nodules at right and one retroareolar nodule at
left. On B, C and D it is possible to observe that the contrast-enhancement
pattern of the breast nodules at right demonstrates characteristics of washout
curve and plateau type 3, sometimes observed in malignant nodules. On E, the
analysis of the kinetic curve of the breast nodule at left demonstrates
characteristics different from the others, showing a type 1 curve, a pattern that
is more frequently observed in benign nodules. Courtesy of Dr. Almir Galvão
Vieira Bitencourt - A.C.Camargo Cancer Center, São Paulo, SP, Brazil.
A 30-year-old female patient presenting with multicentric invasive ductal
carcinoma in the right breast and fibroadenoma in the left breast. On A, one
observes contrast-enhanced, dynamic 3D MIP image with subtraction, demonstrating
the presence of multiple breast nodules at right and one retroareolar nodule at
left. On B, C and D it is possible to observe that the contrast-enhancement
pattern of the breast nodules at right demonstrates characteristics of washout
curve and plateau type 3, sometimes observed in malignant nodules. On E, the
analysis of the kinetic curve of the breast nodule at left demonstrates
characteristics different from the others, showing a type 1 curve, a pattern that
is more frequently observed in benign nodules. Courtesy of Dr. Almir Galvão
Vieira Bitencourt - A.C.Camargo Cancer Center, São Paulo, SP, Brazil.The data provided by dynamic MRI may be utilized for different purposes. Such evaluation
may occur in different phases including diagnosis, staging and treatment response
evaluation, particularly in cases where antiangiogenic drugs need to be evaluated
(. Data in the literature also attribute a relevant role of
perfusion MRI as a prognostic factor and in the evaluation of disease recurrence.
Perfusion MRI has been utilized in the evaluation of different types of tumors as a
tumor hypoxia biomarker, particularly in cases of well vascularized tumors, such as
those in the lungs, uterine cervix, head and neck, breast, liver, musculoskeletal system
and colorectal tumors(. However, the presence of prominent contrast enhancement at the end
of treatment may be associated with a locally aggressive disease, with reduction of
survival rates.Angiogenesis studies have continuously evolved over the last years. The advent of
macromolecular contrast agents allows for the maintenance of such agents for longer
periods in the intravascular spaces. Contrast media containing gadoxetic acid are
examples of such agents in the characterization of focal liver lesions. The development
of substances directed against molecules expressed by neoangiogenic vessels, as the
factor of endothelial vascular growth, is another application field by the perfusion
technique(.
SPECTROSCOPY
Magnetic resonance spectroscopy (MRS) evaluates the distribution and levels of
metabolites normally found in healthy tissues as well as increased levels of metabolites
usually detected in within tumor(.
Creatine, choline, lactate, citrate, N-acetyl aspartate and adenosine triphosphate are
examples of altered metabolites which are commonly found(. This technique can be indicated, for example, to
evaluate breast, prostate and brain lesions(. The main indications
of this method are the following: lesion characterization, selection of biopsy site, and
evaluation of therapeutic response, among others.This technique can be applied in the evaluation of brain lesions. Increased levels of
choline (considered a marker for cell proliferation) in association with decreased
levels of creatine (considered a marker for energetic processes) and decreased levels of
N-acetyl aspartate (considered a neuronal marker) have been found in the evaluation of
brain neoplasms. Combining such levels, it is possible to differentiate, for example,
low-grade from high-grade gliomas( (Figure
8). The application of both conventional MRI and MRS can increases in up to
20% the capability of determining the type and grade of brain tumors. It can
differentiate viable tumor from necrotic area important in the evaluation of the tumor
response. In the presence of response, a decrease in the choline and N-acetyl aspartate
peaks is observed in association with increased levels of lipids and lactate (anaerobic
markers)(.
Figure 8
A 55-year-old male patient. Tumor resection (glioblastoma multiforme) in the left
temporal lobe six months ago, undergoing treatment with radiotherapy and temodal.
MRI scan with advanced techniques was requested for differential diagnosis between
recurrence and radionecrosis in post-gadolinium enhancement areas in the surgical
site. On A, one observes contrast-enhanced T1-weighted image demonstrating
enhancement of the surgical site (arrow). On B, one observes increased perfusion
(arrow) on the rBV map (the ROI in this area, compared with a contralateral area
of healthy white matter, presenting a ratio >2.6, a value which has been
proposed for tumor recurrence. On C and D, the spectroscopy study demonstrates
decreased peak of the metabolite Nacetyl aspartate (NAA) and increased choline
peak (Cho), corroborating the diagnosis. Courtesy of Dr. Leonardo Vedolin -
Hospital Moinhos de Vento, Porto Alegre, RS, Brazil.
A 55-year-old male patient. Tumor resection (glioblastoma multiforme) in the left
temporal lobe six months ago, undergoing treatment with radiotherapy and temodal.
MRI scan with advanced techniques was requested for differential diagnosis between
recurrence and radionecrosis in post-gadolinium enhancement areas in the surgical
site. On A, one observes contrast-enhanced T1-weighted image demonstrating
enhancement of the surgical site (arrow). On B, one observes increased perfusion
(arrow) on the rBV map (the ROI in this area, compared with a contralateral area
of healthy white matter, presenting a ratio >2.6, a value which has been
proposed for tumor recurrence. On C and D, the spectroscopy study demonstrates
decreased peak of the metabolite Nacetyl aspartate (NAA) and increased choline
peak (Cho), corroborating the diagnosis. Courtesy of Dr. Leonardo Vedolin -
Hospital Moinhos de Vento, Porto Alegre, RS, Brazil.In the evaluation of breast lesions, for example, association with choline peak may be
detected in malignant lesions. However, in benign lesions or in healthy breast tissues,
choline levels are either low or undetectable. There are some with this technique that
must be highlighted: in the evaluation of lesions < 2 cm, in breastfeeding women
(considering the presence of a choline peak in the normal breast tissue) or in the
evaluation of some benign lesions such as tubular adenomas, such technique may present
discordant results which must be evaluated together with other exams(.In the evaluation of the prostate spectroscopy obtains metabolic data based on the
relative concentration of endogenous metabolites such as choline, creatine, citrate and,
most recently, polyamine(. The
absolute values of citrate, creatine and choline levels contribute in the identification
of areas suspicious for malignancy and the choline-creatine/citrate ratio demonstrates
equivalence with the Gleason score, allowing for a noninvasive selection of areas for
prostate biopsy and evaluation of the tumor grade(. Thus, spectroscopy
may be employed in the diagnosis of tumor recurrence, in patients treated by
radiotherapy, cryotherapy or surgery(. The routine
utilization of spectroscopy in the evaluation of other neoplasms is still questionable
(Figure 9).
Figure 9
On A, DWI (b = 1000 s/mm2) with high signal intensity in the medial region from 5
o'clock to 7 o'clock (arrow) in the peripheral zone. On B, T2-weighted image
demonstrates a subtle ill defined area (arrow). At spectroscopy (C), increased
choline peak is observed, with decreased citrate peak (ratio choline +
creatine/citrate = 2.7) in the area demonstrated by the ROI of the image on B. On
D, the ADC map demonstrates the same area with low signal intensity (arrow) at 6
o'clock in the peripheral zone. On E, the dynamic contrast-enhanced image
demonstrates enhancement in the medial region (from 5 o'clock to 7 o'clock). On F,
the kinetic curve presents intense and early enhancement (washin) tending towards
rapid clearance (washout). Such parameters represent an area suspected for
malignancy.
On A, DWI (b = 1000 s/mm2) with high signal intensity in the medial region from 5
o'clock to 7 o'clock (arrow) in the peripheral zone. On B, T2-weighted image
demonstrates a subtle ill defined area (arrow). At spectroscopy (C), increased
choline peak is observed, with decreased citrate peak (ratio choline +
creatine/citrate = 2.7) in the area demonstrated by the ROI of the image on B. On
D, the ADC map demonstrates the same area with low signal intensity (arrow) at 6
o'clock in the peripheral zone. On E, the dynamic contrast-enhanced image
demonstrates enhancement in the medial region (from 5 o'clock to 7 o'clock). On F,
the kinetic curve presents intense and early enhancement (washin) tending towards
rapid clearance (washout). Such parameters represent an area suspected for
malignancy.
WHOLE-BODY MRI
Whole-body imaging modalities have been utilized for some time in the evaluation of
cancerpatients(. In the last 10
years, positron emission tomography/computed tomography (PET/CT) has been recognized as
a tool that improved the performance of the clinical evaluation of cancerpatients,
providing a more accurate evaluation and allowing for the selection of the most
appropriate therapeutic option(.
However, the development of new MRI sequences has been improving the utilization of the
method in the evaluation of cancerpatients(. The introduction of echo-planar techniques has allowed the
acquisition of whole-body images by means of different sequences such as T1-weighted,
T2-weighted, STIR and diffusion. The better management of the effects from artifacts
generated by physiological cardiac and respiratory motion has allowed for the
acquisition of good functional images which supplement morphological data usually
obtained by conventional MRI techniques (Figure
10)(.
Figure 10
WBMRI is useful in the detection of metastases, particularly in brain, liver and
bone lesions. On this figure, a 65-year-old female patient presenting with lung
adenocarcinoma in the upper right lobe (long arrow) with metastasis to the left
adrenal gland (short arrow). Coronal WBMRI demonstrates the lesions at the
diffusion-weighted sequence.
WBMRI is useful in the detection of metastases, particularly in brain, liver and
bone lesions. On this figure, a 65-year-old female patient presenting with lung
adenocarcinoma in the upper right lobe (long arrow) with metastasis to the left
adrenal gland (short arrow). Coronal WBMRI demonstrates the lesions at the
diffusion-weighted sequence.Whole-body MRI (WBMRI) is a noninvasive technique free from the risks of ionizing
radiation and with high resolution for soft tissues, which can rapidly acquire
whole-body images. During the scanning, the body is divided into different portions, and
the images are acquired in axial and coronal sections(. Diffusion-weighted whole-body imaging may be applied
to obtain images with body signal suppression. Thus, many organs have their signals
removed and the tumor areas with diffusion are identified as intensely bright or with
high signal intensity(.Studies in the literature have demonstrated that WBRMI is superior to scintigraphy in
the detection of bone metastases as it allows for the visualization of bone marrow
infiltration, while bone scintigraphy can only detect the osteoblastic
activity(. It is a quite sensitive method for assessing bone
lesions in cases of multiple myeloma, as it allows for the direct evaluation of bone
marrow involvement by the tumor. Usually, it is more sensitive than computed tomography
in the evaluation of disease activity. Additionally, it can be employed in the
monitoring of the treatment effectiveness and in the prediction of the treatment
response and prognosis(.For staging purposes, PET/CT has demonstrated accuracy in the evaluation of several
types of tumors, particularly in the case of bronchogenic carcinomas, lymphomas and
colorectal tumors(. Moreover, WBMRI
is also very useful in the detection of distant metastases, especially to the brain,
liver and musculoskeletal system (Figure
11)(. Such tool may be
also applied to evaluate patients with metastases without a known primary tumor. Because
of the absence of ionizing radiation risks, is a good option for early detection tumors
in asymptomatic individuals, when the disease is still curable(.
Figure 11
A 69-year-old male patient presenting with a solid and spiculated mass in the
right upper lobe, incidentally detected at radiography and with histological
diagnosis of adenocarcinoma. At PET/CT (A), there was only normal FDG uptake by
the lesion, with no sign of intrathoracic or distant metastases. WBMRI (B)
demonstrated irregular hypersignal in the lung lesion and in the dorsal
musculature identified on C, D and E, the latter not demonstrated at PET/CT (F).
Biopsy confirmed the diagnosis of pulmonary adenocarcinoma metastasis.
A 69-year-old male patient presenting with a solid and spiculated mass in the
right upper lobe, incidentally detected at radiography and with histological
diagnosis of adenocarcinoma. At PET/CT (A), there was only normal FDG uptake by
the lesion, with no sign of intrathoracic or distant metastases. WBMRI (B)
demonstrated irregular hypersignal in the lung lesion and in the dorsal
musculature identified on C, D and E, the latter not demonstrated at PET/CT (F).
Biopsy confirmed the diagnosis of pulmonary adenocarcinoma metastasis.However, the method presents some limitations such as contraindication for exposure to
magnetic fields. The limitations in the evaluation of the lung parenchyma and the long
acquisition time are being overcome with the development of more advanced apparatuses
and new techniques. Nowadays, a WBMRI scan can be completed in 30 minutes, with
satisfactory resolution of the chest structures and with the capability of screening
peripheral lesions. Some studies report results equivalent to those obtained by
PET/CT(. Additionally, WBMRI may become a useful tool for
patients who do not want to be exposed to ionizing radiation or for those patients on
whom the effects of radiation might cause severe injuries, such as pregnant patients,
children or patients who have been repeatedly exposed during treatment(.
Imaging sequences and WBMRI techniques
Currently there is no consensus about which sequences combination provides greater
WBMRI accuracy, while maintaining reasonable time efficiency(. Notwithstanding the following types
of sequences are normally utilized:1 - Short tau inversion recovery (STIR): This is the most utilized sequence in WBMRI.
A fast STIR sequence with a typical echo train length between 16 and 30 may be
utilized either alone or in combination with other types of sequences(. The advantages of STIR imaging
include the fact that most pathological tissues are rich in protons and have
prolonged T1 times and prolonged T2 relaxation times, with consequential high signal
intensity on STIR sequences(.
Fat suppression with STIR images is stronger and more homogeneous than fat saturation
on T2-weighets images. Coronal STIR sequences may be the only sequences utilized in a
WBMRI scan, but limitations are observed in the depiction of the sternum, ribs,
scapula and skull(. Coronal MRI
is generally less sensitive than axial MRI in the detection of lymph node
disease(.2 - T1-weighted fast spin echo (FSE) sequences may be applied in the coronal plane,
together with the STIR sequence in order to achieve higher specificity in the
detection of spinal cord abnormalities. Coronal T1-weighted fast spin echo sequences
are particularly useful in the evaluation of alterations secondary to radiation
therapy and metastatic lesions in the fatty marrow(.3 - Pre- and post-contrast T1-weighted sequences. According to some authors, such a
sequence should be the base of all WBMRI protocols(. Contrast-enhanced sequences allow for the study of
a region in a single breathhold. The liver, for example, can be evaluated in the
arterial and venous phases. At the end, the rest of the body can be evaluated for
screening metastatic lesions(.
The utilization of gadolinium-based contrast agents improves the sensitivity,
specificity and diagnostic accuracy of the method. Its utilization facilitates the
combination of local staging and evaluation of metastatic disease in a single
scan.4 - Single-shot sequence: The application of such sequence in both planes, axial and
coronal, may be useful in the presence or suspicion of gastrointestinal disease. It
has a short acquisition time and may be easily incorporated in the WBMRI protocol,
without compromising time efficiency of the method.5 - Steady-state free precession sequence: A fast sequence of images like this was
utilized in a small group of only five patients to detect liver and lung metastases
with diameters > 8 mm(. This
type of sequence provides good morphological data and outlines vessels with good
accuracy.The chest and abdominal imaging provided by the WBMRI is particularly challenging due
to respiratory motion and intestinal peristaltic motion. These may be obtained
applying respiratory compensation techniques with extended acquisition time.
Antiperistaltic drugs could help to reduce the intestinal motility. It is important
to note that in cases where the chest or the abdomen are the location of a primary
tumor or area of neoplastic disease, the WBMRI scan is generally performed according
to a dedicated imaging protocol including the utilization of respiratory compensation
techniques and, sometimes, the administration of anti-peristaltic drugs.
PET/MRI
Over the past two decades, the continuous utilization of PET/CT in oncology as well as
the introduction of WBMRI techniques have led to the fusion of images obtained by both
methods (Figure 12) and the development of hybrid
PET/MRI equipment(. A limitation that impaired the association of both
modalities in a single facility was the fact that the photomultipliers utilized in PET
did not operate appropriately within or near the magnetic field. Another limitation was
the presence of metalic material in the surface coils, causing interference with the
gamma rays and attenuation at PET/CT(. However, with technological developments obtained in the recent
years, some of those barriers were overcome and the first facilities now are available
for clinical application (.
Figure 12
A 71-year-old male patient presenting with squamous cell carcinoma in the right
upper lobe, with no sign of metastatic lesions at PET/MRI. In this case, there was
a fusion of the coronal MRI T1-weighted image with the functional image acquired
with FDG-PET/CT.
A 71-year-old male patient presenting with squamous cell carcinoma in the right
upper lobe, with no sign of metastatic lesions at PET/MRI. In this case, there was
a fusion of the coronal MRI T1-weighted image with the functional image acquired
with FDG-PET/CT.The clinical applications of PET/MRI are under continuous investigation and advances in
this field have been documented. Recently published data suggest that PET/MRI adds
greater value in the assessment of cancerpatients. Some specific advantages are
attributed to PET/CT in the detection of bone and lymph node metastases, and to MRI in
the detection of brain and liver metastases(. Furthermore, the advantage of comprehensively scanning the
whole body in a single moment would justify the combined utilization of both tools.
However, a consensus on the indications and actual benefits in clinical practice is
still to be established.
CONCLUSION
We currently live in the era of individualized treatment. Genetic and intrinsic factors
of the tumor are decisive in the evolution of the disease and in the therapeutic
approach. The evaluation of functional parameters by MRI is increasing in the clinical
set of cancerpatients allowing a better understanding of the disease complexity and
therapeutic management, with a positive impact on such group of patients.
Authors: Dow-Mu Koh; Matthew Blackledge; Anwar R Padhani; Taro Takahara; Thomas C Kwee; Martin O Leach; David J Collins Journal: AJR Am J Roentgenol Date: 2012-08 Impact factor: 3.959