Diffusion-weighted and Perfusion MR Imaging for Brain Tumor Characterization and Assessment of Treatment Response- An Overveiw

JAMESM.PROVENZALE,MD SRINIVASANMUKUNDAN,PHD,MD DANIELP.BARBORIAK,MDRSNA 2006

Introduction

Perfusion MR Imaging of Brain Tumors: An Overview

Perfusion imaging of brain tumors has been performed by using various tracer and nontracer modalities and can provide additional physiologic and hemodynamic information

Tumor vascular perfusion parameters obtained by using MR perfusion

1. tumor grading, prognosis, and treatment response I

2. differentiating treatment/radiation effects

3. non-neoplastic lesions from neoplasms

DW IMAGING & DTI Brownian Motion

ADC: Apparent diffusion coefficient : represent microscopic water molecule diffusability in presence of factors that restrict Diffusion

Eg:/ cell memberane, viscocity

In tumors with necrosis, surrounding oedema etc.

DTI , diffusion-tensor imaging provides a sensitive means to detect alterations in the integrity of white matter structures.

Whitematter abnormalities can be seen on diffusion-tensor images that are not evident on routine MR image

DTI tractography can provide guidelines fro surgical intervention and management.

Provide WM tract abnormalities very distal or far from Primary lesion.

Perfusion MR Imaging of Tumors ANGIOGENESIS : In active (growing) lesions .

Lack of maturity. Increased permeability to macromolecules.

Indicator-dilution model

Fick principle;assumes a simple scheme in which the concentration of an agent is a function of the contrast agent volume and the vascular volume.

This scheme does not adequately take into account the effect of extravasation of the agent.

Pharmacokinetic (multicompartment) model

scribes a more complex interaction between two compartments in the tumor:

the intravascular space and the extravascular extracellular space (EES)

Increased vessel tortuosity, immaturity, and permeability (seen in high-gradetumors) lead to an increase in the permeability–surface area product.

. When a dysprosium based contrast agent is used, the rate of administration was found to affect the shape of the time-enhancement curve

But not the area under the signal intensity–time curve, which is proportional to the relative cerebral blood volume (rCBV)

Regions of high rCBV are thought to reflect areas of high capillary density,which is a reflection of tumor aggressiveness.

Dynamic susceptibility-contrast (DSC) approaches are first-pass techniques that are T2- or T2*-weighted.

At high concentrations, the contrast agent induces substantial T2* shortening,

First in loss and then in recovery of signal in the tumor bed as the agent is redistributed or diluted.

DSC MR imaging can be performed by using either a gradient-echo or a spin-echo pulse sequences

GE-DSC is sensitive to larger vessels as in veins

SE-DSC is sensitive to smaller cappilaries; so more useful in assesement of the tumor

These methods can be safely used when the rate of vascular leakage is low.

When the rate of leakage is high, rCBV mapping results can be underestimated

Arterial spin labeling *is an endogenous contrast approach in which the patient’s own blood is magnetically labeled with an MR prepulse prior to the blood’s entry into the imaging volume.

Perfusion parameters rCBV: almost all studies have concentrated on rCBV assessment

A number of rCBV measurement methods exist,

1. placement of a single region of interest and calculation of the mean of repeated rCBV measurements

but few studies have been performed on the reproducibility of rCBV measurements using this technique

2. Placing multiple regions of interest .

3. Permeability can also be assessed with the use of DSC images, which would allow one to obtain both permeability and rCBV measurements from the same infusion of contrast.

The technique is not considered to be valid under conditions in which a very high degree of contrastmaterial leakage is present, which is a limitation in many cases

Perfusion and DW MR Imaging forTumor Characterization

, higher grade tumors would be expected to have higher rCBV

rCBV has typically been calculated by comparing the pathologic region to a corresponding region in the contralateral hemisphere.

Most investigators have chosen to use a normal-appearing region in contralateral white matter as a control region, which generally differs in location from patient to patient.

Findings:

1. Values in high-grade tumor are typically seen to be at or near rCBV values in gray matter.

2. some evidence exists that nonglial neoplasms (eg, lymphoma) appear to have lower rCBV than do high-grade glialneoplasms.

Relative cerebral blood flow and mean transit time, but they are less valuable in the evaluation of brain tumors

high-grade tumors had heterogeneous rCBV maps with regions of high rCBV, whereas low-grade lesions had only low rCBV.

MR Perfusion as guide for Stereotactic Biopsy Planning

More accurate preoperative grading of primary brain tumors could have a major effect on the lives of patients with brain tumors, perhaps by leading to fewer biopsies.

Site to could be selected on basis of rCBV maps and areas with high rCBV values are biopsied.

Advantage :

1. Improves the chance of a positive accurate biopsy

2. Reduces no of biopsies

3. In Post operative recurrence suspected cases rCBV maps can provide information regarding cellularity without a repeat Biopsy

Perfusion and DW MR Imaging forAssessment of Tumor Therapy

rCBV is thought to correspond to microvessel density, early response to antiangiogenesis therapy might manifest as a decrease in rCBV.

Alternatively, because some angiogenesis factors are permeability promoters, a decreased rate of contrast material leakage might be an early indication of response to antiangiogenesis therapy.

monitor tumor angiogenesis and assess the response to antiangiogenic therapies.

A few initial studies have used dynamic contrast-enhanced MR to assess for tumor response to therapy.

In DWI

An increase in ADC values compared to pre-therapeutic values confirms response(i.e reduced cellularity)

Studies of patients with brain tumors have shown that increases in water diffusion generally indicate a positive response to therapy

Radiation-induced Necrosis versus TumorRecurrence

The two entities can usually be distinguished by using positron emission tomography with fluorine 18 fluorodeoxyglucose.

. Because recurrent high-grade tumor is characterized by angiogenesis (and typically high rCBV) and tumor necrosis is generally less rCBV values.

Also can determine difference between normal brain and low-grade astrocytoma after radiation treatment.

DWI has no or Limited role in assessment of Post Radiotherapy changes.

One Study suggested when used in tandem with MRSpectroscopy it improves Positive Predictive value.

MR perfusion v/s CT perfusion Perfusion CT and dynamic contrast-enhanced MR techniques were compared in the same patient, a relatively good correlation was seen between the two techniques with regard to the tumoral regions of highest permeability and regions of highest rCBV.

DW MR Imaging for Definition of TumorMargins

In Morphologoic assessment of tumors usually unenhanced area adjacent to tumor is considered the free margin of the tumor.

This model of tumor structure is oversimplistic for primary glial tumors, because tumor cells areknown to extend into the unenhancing region of peritumoral edema and even into normal-appearing white matter far from the primary lesion.

Tumors may have both enhancing and nonenhancing zones ; or even completely non enhancing.

A number of studies have shown that ADCs in peritumoral edema are higher for metastases than for primary cerebral tumors

Some authors suggested that high-grade glioma could be differentiated from metastases and low- grade glioma by using measurements in perilesional edema of a so called tumor infiltration index, which is based on the relationship of fractional anisotropy to mean diffusivity

Several investigators have studied the application of DW and diffusion-tensor imaging to delineation of the tumor margin. By and large, the results of these studies do not correlate the location of DW or diffusion-tensor imaging abnormalities with histopathologically defined tumor boundaries; rather, the approach taken has been to demonstrate differences in peritumoral characteristics in high- grade liomas , which show some degree of tumor infiltration into non-ehancing regions adjacent to the enhancing mass as compared with low-grade gliomas, metastases, and meningiomas.

DW imaging with a high b-value (generally in the range of 3000–4000 sec/mm 2 ) allows the characteristics of water diffusion to be studied in more detail.

With this technique, diffusing water molecules have been studied in different pools

Eg: slow diffusion , fast diffusing pools,

Help in differentiating tumor tissue from Peri-tumoral oedema.

In general a tumor cellularity has an inverse correlation with the ADC values

i.e more cellular : lower ADC values.

ADC measurements have been found to be decreased in lymphomas relative to measurements in other intracranial tumors such as high-grade gliomas.

In Vivo Perfusion Imaging versus Histopathology

Current standard for tumor grading is histopathologic as sessment of tissue.

inherent limitations : sampling error, interobserver variation, and a wide variety of

classification systems that are available*

Many are region variable especially large tumors with heterogenous enhancement.

Unless excision Biopsy done ; nothing can be confirmed especially regarding vascularity of the lsesion.

Higher the grade more herterogenity in tumor less specificity in histo path alone

These limitations canfrequently result in inaccurate classification and grading of

gliomas due to sampling errors

Brain tumor angiogenesis is a continuously evolving process that can also be affected by various treatment modalities.

in vivo perfusion imaging that can be repeated (unlike invasive procedures such as surgical excision or biopsy)

Continued evolution of these tumors as well as treatment response.

MR PERFUSION v/s FDG-PET A quantitative rCBV as calculated from a perfusion MRI scan might be superior to the Lmax/Rmax ratio as derived from 18F-FDG and 11C-MET PET in order to distinguish a recurrence of high-grade glioma from radiation necrosis.

Yong Hwy Kima, So Won Ohb, You Jung Limc, Chul-Kee Parka, e, , , Se-Hoon Leed, Keon Wook Kangb, Hee-Won Junga, Kee Hyun Changc

Clinical Neurology and Neurosurgery

Volume 112, Issue 9, November 2010, Pages 758–765

Fourteen enhancing lesions could be classified as progressing (11) or regressing (three). An empirical threshold of 2.0 ml/100 g for rCBV allowed detection of regressing lesions with a sensitivity of 100 % and specificity of 100 %. FDG-PET and DCE-MRI agreed in classification of tumor status in 13 out of the 16 cases where an FDG-PET classification was obtained. In two of the remaining three patients, MRI follow-up and histology was available and both indicated that the DCE-MRI answer was correct.

Vibeke A. Larsen, Helle J. Simonsen, Ian Law, Henrik B. W. Larsson, Adam E. Hansen Neuroradiology

March 2013, Volume 55, Issue 3, pp 361-369

OTHER APPLICATIONSABSCESS V/S TUMOR

Perfusion MRI may allow the differentiation of pyogenic brain abscess from cystic brain tumors, making it a strong additional imaging modality in the early diagnosis of these two entitie

In perfusion-weighted images, the capsular portions of the abscesses demonstrated low colored areas compared with the normal white matter and the rCBV ratio calculated was 0.76 ± 0.12 (mean ± SD).

The rCBV values in high-grade gliomas and metastases were 5.51 ± 2.08 and 4.58 ± 2.19, respectively. The difference between abscesses and cystic tumors was statistically significant Erdogan, Cuneyt MD*; Hakyemez, Bahattin MD*†; Yildirim, Nalan MD*; Parlak, Mufit MD*

September/October 2005 - Volume 29 - Issue 5 - pp 663-667

Neuroimaging: Original Article

SUMMARY Measurement of rCBV by using both dynamic contrast-enhanced (T1-weighted) and dynamic susceptibility contrast (T2*-weighted) approaches have shown good correlation with World Health Organization tumor gradES

A rCBV value of >2 suggests high cellular vascularity.

Diffusion-weighted (DW) imaging may allow the cellularity of tumors to be graded noninvasively*

A high ADC score suggest less cellularity and can be used to monitor Tumor Response to Therapy.

Overall tissue characterestics can be assessed more easily than Histopathology.

Studies of patients with brain tumors have shown that increases in water diffusion generally indicate positive response to therapy.

Perfusion and DW MR imaging are providing insights into tumor behavior that are not available from conventional MR imaging and Important for assessment of tumor response to therapy than for diagnosis.

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TAPV-R - SNowman APVR can be classified into four types (in decreasing order of frequency) depending on the site of anomalous venous union 1:

Type I: supracardiac

anomalous pulmonary veins terminate at the supracardiac levelpulmonary veins converge to form a left vertical vein which then drains to either brachiocephalic vein, SVC or azygous vein

Type II: cardiac

pulmonary venous connection at the cardiac leveldrainage is into the coronary sinus and then the right atrium

Type III: infracardiac

The pulmonary veins join behind the left atrium to form a common vertical descending vein

the common descending vein courses anterior to the oesophagus passes through the diaphragm at the oesophageal hiatus and then usually joins the portal system

drainage is usually into the ductus venosus, hepatic veins, portal vein or IVC

Type IV: mixed pattern

Pellegrini-Stieda lesion Pellegrini-Stieda (PS) lesions are ossified post-traumatic lesions at (or near) the medial femoral collateral ligament adjacent to the margin of the medial femoral condyle. One presumed mechanism of injury is a Stieda fracture (avulsion injury of the medial collateral ligament at the medial femoral condyle). Calcification usually begins to form a few weeks after the initial inju

Lissencephaly Congenital cortical malformations characterised by absent or minimal sulcation.

type I (classic) lissencephaly

type II (cobblestone complex) lissencephaly

Type I (classic) lissencephaly can apear as the classic hour glass or figure-8 appearance or with a few poorly formed gyri (pachygyria) and a smooth outer surface. It is usually associated with band heterotopia.

Type II lissencephaly on the other hand has a microlobulated surface referred to cobblestone complex. There is not band heterotopia and the cortex is thinner than type I.