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STATE OF THE ART PROSTATE MR IMAGING

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Brachytherapy alone not appropriate. Clinical Application: MR Targeted, TRUS-Guided Biopsies ... Metabolic Response to Brachytherapy. 107 wks. red = abnormal ... – PowerPoint PPT presentation

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Title: STATE OF THE ART PROSTATE MR IMAGING


1
STATE OF THE ART PROSTATE MR IMAGING
2
STATE OF THE ART PROSTATE MR IMAGING
  • DYNAMIC CONTRAST-ENHANCED MRI (DCE-MRI)
  • LYMPHOTROPIC SUPERPARAMAGNETIC NANOPARTICLES
    ENHANCED MRI
  • MR SPECTROSCOPIC IMAGING (MRSI)

3
ENDORECTAL COIL FOR HIGH-RESOLUTION ANATOMIC
ANALYSIS
  • PROSTATE GLAND
  • PROSTATE CAPSULE
  • SEMINAL VESICLES
  • NEUROVASCULAR BUNDLES
  • DENONVILLIERS FASCIA
  • PARARECTAL LYMPH NODES

4
BLOOD FROM RECENT BIOPSY
  • COMPLICATES INTERPRETATION OF MR ANATOMIC IMAGING
  • COMPLICATES INTERPRETATION OF MRSI
  • COMPLICATES INTERPRETATION OF DCE-MRI

5
PELVIC MRI
  • LYMPH NODE ANALYSIS
  • VASCULAR DISEASE
  • OTHER MASSES

6
DYNAMIC CONTRAST-ENHANCED MRI
  • Anatomic imaging provides only one index of
    biologic activity
  • Some therapies, such as antiangiogenic and
    vaccines therapies, are expected to be cytostatic
    and thus may not produce objective responses in
    tumor size

7
DYNAMIC CONTRAST-ENHANCED MRI
  • DCE-MRI -- acquisition of serial MR images
    before, during, and after the administration of
    an IV contrast agent
  • Resulting signal intensity measurements of the
    tumor reflect a composite of tumor perfusion,
    vessel permeability, and the volume of the
    extravascular-extracellular space
  • DCE-MRI, in conjunction with traditional MRI,
    provides functional and detailed morphologic
    information in the same study

8
DYNAMIC CONTRAST-ENHANCED MRI
  • DCE-MRI has been employed for tumor detection,
    characterization, staging, and therapy monitoring
  • Cancers demonstrate typical enhancement kinetics
    rapid and high amplitude wash-in followed by a
    relatively rapid wash-out. This pattern can be
    used to distinguish malignant masses from benign
    lesions or normal tissue, which enhance slowly
    and washout slowly

9
DYNAMIC CONTRAST-ENHANCED MRI -- FALSE POSITIVES
AND NEGATIVES
  • Microscopic disease may still be present even
    when DCE-MRI shows no evidence of tumor
  • Some malignant processes can mimic benign
    contrast kinetics, and some benign processes
    (e.g., inflammation) can mimic malignant contrast
    kinetics
  • It is thus important to have histopathologic
    correlation at the initial study to determine the
    particular contrast kinetics of a tumor

10
DYNAMIC CONTRAST-ENHANCED MRI
  • Monitoring of cancer therapy is another important
    role of DCE-MRI
  • DCE-MRI provides direct and early evidence of a
    therapeutic effect by demonstrating changes in
    the enhancement curves (slower initial
    enhancement, decreased amplitude, slower
    wash-out)
  • Failure of particular areas of the tumor to
    respond to therapy implies the presence of
    resistant clones

11
DYNAMIC CONTRAST-ENHANCED MRI
  • Tumors with higher initial permeability often
    respond better to chemotherapy than tumors with
    lower permeabilities, as it is possible to
    deliver more cytotoxic therapy to these lesions
  • More permeable tissues may be better oxygenated
    and therefore initially more radiosensitive
  • Changes on DCE-MRI may be non-predictive the
    therapy may induce physiologic changes in the
    tumor without affecting patient survival

12
DYNAMIC CONTRAST-ENHANCED MRI
  • Angiogenesis is now considered one of the major
    events that must occur if a tumor is to grow
    beyond several millimeters in diameter
  • If tumors are to grow beyond this size, they must
    induce surrounding vessels to create neo-vessels,
    i.e., angiogenesis

13
DYNAMIC CONTRAST-ENHANCED MRI
  • Angiogenic inhibitors reduce both the number of
    vessels (especially nonfunctional vessels) and
    their permeability on DCE-MRI
  • Some therapies, such as antivascular endothelial
    growth factor antibody, are specifically directed
    against a growth factor, VEGF, and are thought to
    regulate vascular maturation, and thus
    permeability
  • Such changes are predicted to occur early after
    treatment

14
DYNAMIC CONTRAST-ENHANCED MRI
  • More conventional therapies can also be monitored
    with DCE-MRI because vessel loss is a final
    common pathway for many therapies
  • Cytotoxic chemotherapy and vaccine immunotherapy
    result in changes in enhancement kinetics within
    a tumor

15
DYNAMIC CONTRAST-ENHANCED MRI
  • Therapeutic radiation can also be monitored
    because decreased vascularity is anticipated with
    successful treatment early after therapy
  • A form of angiogenesis induced by radiation
    fibrosis may be seen months after initial
    therapy, leading to paradoxical increases in
    vessel permeability
  • Local therapies, such as cryotherapy and
    radiofrequency ablation, can also be monitored
    with DCE-MRI

16
DYNAMIC CONTRAST-ENHANCED MRI
  • Prostate gland is particularly difficult to
    evaluate
  • Heterogeneous gland with its central regions
    prone to hyperplastic changes and tumors, both of
    which display a range of angiogenesis
  • The peripheral zone is normally relatively
    hypovascular
  • Low grade tumors also tend to be relatively
    hypovascular and thus are difficult to detect
    against the background of normal contrast
    enhancement

17
DYNAMIC CONTRAST-ENHANCED MRI
  • Nonetheless, contrast-enhanced MRI using rapid
    bolus techniques have been reported to be more
    sensitive to tumors and are a useful adjunct to
    T2-weighted scans in tumor localization and
    staging.

18
LYMPHOTROPIC SUPERPARAMAGNETIC NANOPARTICLES
ENHANCED MRI
  • NANOPARTICLES WITH IRON OXIDE CORE ARE SLOWLY
    EXTRAVASATED FROM THE VASCULAR SPACE INTO THE
    INTERSTITIAL SPACE
  • TRANSPORTED TO LYMPH NODES VIA LYMPHATICS

19
LYMPHOTROPIC SUPERPARAMAGNETIC NANOPARTICLES
ENHANCED MRI
  • NANOPARTICLES INTERNALIZED BY MACROPHAGES IN
    LYMPH NODES
  • INTRACELLULAR IRON-CONTAINING NANOPARTICLES CAUSE
    CHANGES IN MAGNETIC PROPERTIES DETECTABLE BY MR
    IMAGING

20
LYMPHOTROPIC SUPERPARAMAGNETIC NANOPARTICLES
ENHANCED MRI
  • MRI PERFORMED BEFORE AND 24 HOURS AFTER IV
    ADMINISTRATION OF THE NANOPARTICLES
  • NODAL INFILTRATION BY TUMOR CAUSES LESS MAGNETIC
    SUSCEPTIBILITY CHANGE

21
LYMPHOTROPIC SUPERPARAMAGNETIC NANOPARTICLES
ENHANCED MRI
Sensitivity
Specificity
Accuracy
PPV
NPV
Per Patient
Per Individual Lymph Node
LN Short Axis 5-10 mm
LN Short Axis lt 5 mm
N ENGL J MED 2003 3482491-2499
22
COMBINED ANATOMIC AND METABOLIC IMAGING OF
PROSTATE CANCER -- MRI/3D MRSI
  • MRSI PROVIDES A NON-INVASIVE METHOD OF DETECTING
    SMALL METABOLITES WITHIN THE CYTOSOL OR IN THE
    EXTRACELLULAR SPACES OF THE PROSTATE GLAND
  • PERFORMED IN CONJUNCTION WITH HIGH RESOLUTION
    ANATOMIC IMAGING

23
COMBINED ANATOMIC AND METABOLIC IMAGING OF
PROSTATE CANCER -- MRI/3D MRSI
  • INITIAL HUMAN STUDIES HAVE FOCUSED ON MRI/MRSI ON
    1.5 T SYSTEMS
  • VALUE OF THIS COMBINED APPROACH HAS BEEN SHOWN IN
    THE LITERATURE
  • WHILE ALREADY VALUABLE, COMBINED MRI/MRSI IS
    STILL IN ITS INFANCY. DRAMATIC IMPROVEMENTS IN
    SPATIAL RESOLUTION, CHEMICAL SPECIFICITY, AND
    BIOLOGIC INFORMATION ARE POSSIBLE

24
RADIOLOGIC TESTS FOR PROSTATE CANCER?
  • LOCAL STAGING (FOR EXAMPLE, EXTRACAPSULAR
    EXTENSION OR SEMINAL VESICLE INVASION) BY TRUS
    AND MRI IS FELT TO BE IMPORTANT -- DETERMINES
    WHETHER THE PATIENT GETS CURATIVE LOCAL THERAPY
    OR PALLIATIVE SYSTEMIC THERAPY
  • LOCATION AND EXTENT OF CANCER WITHIN THE PROSTATE
    GLAND IS BECOMING INCREASINGLY IMPORTANT DUE TO
    THE EMERGENCE OF FOCAL PROSTATE CANCER THERAPIES,
    AND FOR THE SELECTION AND RISK STRATIFICATION OF
    PATIENTS IN CLINICAL TRIALS

25
MRI Methods
  • Multi-planar high-resolution T2 weighted images
    are acquired through the prostate and surrounding
    structures in order to assess the location,
    spatial extent, and spread of prostate cancer.
  • T1 weighted images are acquired through the
    prostate gland and pelvis in order to assess for
    the presence of post-biopsy hemorrhage within the
    prostate gland and metastases to pelvic bones and
    lymph nodes.

26
MRI Staging of Prostate Cancer
  • MRI alone has good accuracy in detecting seminal
    vesicle invasion (96).

Radiology 1994193703-709
27
MRI Lacks Specificity for Localizing Cancer
within the Prostate
High Resolution MRI has demonstrated good
sensitivity (79) but low specificity (55) in
determining tumor location due to a large number
of false positives.
Radiology 1994193703-709
28
MRSI Metabolic Identification of Prostate Cancer
Prostate Cancer
Creatine
Creatine
3.0
PPM
2.0
2.5
Cancer
Healthy
29
Interpretation of Combined MRI/MRSI Data
The output of the MRI/MRSI exam are arrays of
0.3cc spectra and corresponding high resolution
anatomic images.

The interpretation of the data requires a
knowledge of what constitutes a useable spectra,
how spectra change with zonal anatomy and age,
and other complicating factors such as
post-biopsy hemorrhage, and contamination from
surrounding tissues.
Portion of the 3-D MRSI spectral array
30
Contamination from Different Tissues Within the
Prostate
creatine
Choline
Citrate
Prostate Cancer
A voxel containing both healthy glandular tissue
and cancer may look like this elevated choline
to creatine but normal levels of citrate
31
Complications to the Interpretation of Prostate
Spectra
Post-biopsy artifact
T1 WI
At the time of this previous study, biopsy
hemorrhage was observed in 28 of patients studied
Radiology 1998206785-790
32
Appearance of Spectra In Regions of Hemorrhage
Patients have demonstrated both metabolic atrophy
and changes in their metabolite levels in regions
of extensive hemorrhage, particularly early after
biopsy
3 weeks after biopsy
tumor
atrophy
Cho Cr PA
tumor
tumor
citrate
atrophy
atrophy
33
Hemorrhage Induced Changes in Healthy Tissue
A
T1 weighted MRI
CC/C0.81
Choline
4 weeks after biopsy
Citrate
CC/C0.22
12 weeks after biopsy
Choline
Citrate
By requiring elevated choline be present when
there is hemorrhage can reduce over-calling cancer
Li, ISMRM 2002
5.0
3.5
4.0
3.0
PPM
2.0
2.5
34
MRI/MRSI Data Summary
Up to 1024 spectra per study - Need for summary
images
MRSC/UCSF - Proton MRS Study
35
Assessment of Cancer Aggressiveness (Grade)
Neoplasia 20002(1-2) 166-169
36
STAGING PREDICTION OF ECEROC Analysis (187
patients)
1
Sensitivity
0.75
0.5
MRI/MRSI
0.25
TRUS
Biopsy
0
0
0.25
0.5
0.75
1
1 - Specificity
37
Localization of Cancer to a Sextant of the
Prostate by MRI/MRSI
MRI/MRSI data can be combined to provide both
high specificity or sensitivity in localizing
cancer to a prostatic sextant depending on the
clinical question.
  • A specificity of up to 91 was obtained when both
    MRI and MRSI were positive for cancer. Add
    positive sextant biopsy results - 98.
  • A sensitivity of 95 was obtained when MRI or
    MRSI were positive for cancer. With the addition
    of positive sextant biopsy, the sensitivity
    remains high at 94.
  • A significant (Plt0.05) improvement in overall
    accuracy ( 80) over MRI and biopsy alone.

Journal Urology 2000, 164(2) 400-404 Radiology
1999 213473-480
38
MRI/MRSI Current Clinical Uses
  • Therapeutic Selection - individualized therapy (
    60 of patients)
  • Cancer Diagnosis - men with rising PSA but
    negative biopsies ( 10 of patients)
  • Therapeutic Monitoring ( 30 of patients)
  • Early identification of failure
  • Time course of response


39
Individualized Therapeutic Selection
C
  • MRI/MRSI concordant for a large volume of
    aggressive cancer with spread outside the capsule
    and seminal vesicle invasion

Cho
Cr
  • Brachytherapy alone not appropriate

40
Clinical Application MR Targeted, TRUS-Guided
Biopsies
The sensitivity of TRUS guided biopsy is reduced
in large prostates and when the cancer is located
in difficult locations such as the apex of the
gland or in the anterior or lateral aspects of
the gland
PSA - 12 ng/ml Two prior negative biopsies
Journal Urology 2000, 164(2) 400-404
41
The addition of the metabolic information
provided by MRSI becomes even more important
after therapy since the contrast between healthy
tissue and cancer is reduced on MRI
Monitoring Therapy Radiation Therapy
Tumor
Pre-Therapy
42
MRSI has Demonstrated the Ability to Identify
Cancer Metabolically after Therapy
Atrophy or Necrosis
Radiology 1996 200489-96
43
Successful Therapy Complete Metabolic Atrophy
Pre-therapy
Post-therapy
44
Unsuccessful External Beam Radiation Therapy
Cancer
Cancer
Atrophy
Cancer
A T2-weighted MR image and spectral array taken
from the midgland of a 55-year-old prostate
cancer patient with a current PSA of 0.6 ng/ml
who had IMRT in June of 2000. Note the metabolic
atrophy consistent with effective therapy in the
right side of the gland, and residual metabolism
on the left side of the gland. The presence of
cancer in the left lateral aspect of the prostate
gland was subsequently confirmed by ultrasound
guided biopsies.
45
Unsuccessful Hormone Deprivation Therapy
21 months of combined hormone deprivation therapy
- PSA - 0.4
46
Time Course of Metabolic Response to Brachytherapy
red abnormal metabolism
47
Time-Course of Metabolic Recovery After Cessation
of Therapy
77 year old patient Gleason 34 1 year of
combined Lupron and Casodex PSA at time of scan -
0.4 ng/ml
Metabolic Atrophy
48
CONCLUSIONS
  • MRI/MRSI HAS BEEN ESTABLISHED AS A POWERFUL
    IMAGING TECHNIQUE FOR PRE- AND POST-TREATMENT
    ANALYSIS
  • GREAT PROMISE FOR LYMPHOTROPIC SUPERPARAMAGNETIC
    NANOPARTICLES TO ASSESS LYMPH NODE METASTASES
  • DCE-MRI IS RELATIVELY NEW IN THE EVALUATION OF
    PROSTATE CANCER, AND ITS CLINICAL UTILITY IS YET
    TO BE DETERMINED
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