0:01

So as I said previously, we start with the separation

0:05

of those tumors that are IDH mutant from those

0:09

that are IDH wild type

0:11

with the IDH wild type defining the glioblastoma.

0:14

So let's talk now about IDH mutant tumors.

0:18

So the ID IDH mutant tumors can be separated

0:24

histopathologically and

0:25

by molecular genetics into different grades.

0:29

The molecular genetic marker that defines grade four

0:33

for an I DH mutant glioma is this

0:37

CDKN two A slash B deletion.

0:41

So CDKN two A B deletion defines

0:45

WHO grade four molecular basis

0:49

for calling it a grade four tumor.

0:53

Again, this is going to be an astrocytoma based on

0:57

the presence of the A T RX mutation.

1:00

Um, but it will be separated based on that

1:04

molecular deletion if the tumor also shows necrosis

1:09

and microvascular proliferation.

1:11

As I mentioned, the histological hallmarks

1:14

of a high grade tumor.

1:16

It also will define a tumor as grade four.

1:21

We mentioned that after the separation into

1:25

IDH mutant, we then have

1:27

to separate things into astrocytomas versus ogden gliomas.

1:31

And the one P 19 Q code deletion is

1:33

what defines the algo DRO glioma.

1:36

There's another molecular marker which is very important,

1:39

which does not have to do with the histopathology

1:42

and that is the MGMT promoter methylation.

1:45

Depending upon that state, the tumor will be more

1:49

or less sensitive to both temodar therapy, part of

1:54

that chemotherapy for gliomas as well as more sensitive

1:58

to radiation treatment.

2:00

However, the MGMT promoter status also

2:05

may lead to a greater

2:06

or lesser degree of the issue of pseudo-progression.

2:10

That is where the imaging looks worse even though the

2:14

patient is getting better.

2:16

So we'll talk about that shortly.

2:19

So we now take WHO 2016 classification

2:24

and we convert it to WHO 2021 classification.

2:28

And you notice that we have astrocytomas,

2:31

which are IDH mutant

2:34

and they may be grade two, grade three, grade four.

2:37

Remember that the grade ones are those sort

2:39

of benign ones such as pilocytic astrocytoma.

2:43

And then we have the glioblastoma defined by IDH wild type.

2:47

And then we have the ones that are defined

2:50

by the one P 19 Q code deletion,

2:53

which are our allendra gliomas.

2:56

And those two are separated into grade

2:58

Two and grade three on the basis of histology.

3:03

Why is this all important?

3:05

Well, as you know,

3:06

there's a much different prognosis when one has a

3:10

glioblastoma versus a non glioblastoma astrocytoma

3:14

IDH mutant tumor versus those

3:18

that have the oligodendroglioma.

3:20

So if you had

3:21

to pick a glioma in the brain, what would you pick?

3:25

Oligodendroglioma you see in the purple

3:27

that it has the best long-term survival compared

3:31

to astrocytoma

3:33

and the one that we know which is

3:35

the worst prognosis is the glioblastoma.

3:39

So although we have made progress with glioblastoma,

3:42

as you can see this is a paper from 2023

3:46

and we're still at a point where not very many people

3:50

make it out that uh, to a far distance with glioblastoma.

3:56

What do these look like?

3:58

Well, these can look in a variety of different,

4:02

uh, appearances.

4:03

They may or may not show enhancement.

4:06

This is a grade two IDH mutant tumor.

4:10

It does not show enhancement.

4:11

However, some of the grade two

4:14

and grade three tumors will show contrast enhancement.

4:18

In general, no restricted diffusion

4:22

and you can see that here and no increased perfusion.

4:26

So we generally say that the grade of the tumor does vary

4:30

with the values of the A DC maps as well as the degree

4:35

of hyperperfusion.

4:38

This is another uh, example.

4:40

In this example we have a CT flare,

4:45

post gadolinium enhanced scan, diffusion weight scan,

4:48

and our perfusion weight scan.

4:50

This is an A DC map

4:52

and as you can see here,

4:54

a well-defined lesion which is not showing

4:57

contrast enhancement and the profusion

5:01

map shows, if anything

5:04

lower profusion within the tumor.

5:07

So how do you look at these uh, maps?

5:10

You know that the white matter

5:12

has less perfusion than the gray matter.

5:15

So on this map, yellow is less perfused than green

5:20

and therefore this tumor is actually showing, um,

5:24

diminished perfusion.

5:25

So you can either look at what's happening in the ventricle

5:27

to see absence of enhancement and absence of profusion,

5:32

or you can look at the difference between gray matter

5:35

and white matter in order

5:36

to get your gray scale on these color maps of uh, perfusion.

5:41

And you notice also that there aren't areas of dramatic

5:45

decrease in the A DC on the vast majority of this tumor.

5:50

This is a patient who has an IDH mutant grade three.

5:54

So as we increase in the grade,

5:57

we may see increasing enhancement.

5:59

We may see increasing necrosis, potentially we may see

6:05

also an increase in the perfusion.

6:08

So here we have a patient,

6:10

it's infiltrating ill-defined heterogeneous signal intensity

6:16

and it has some areas

6:17

that show contrast enhancement on the post

6:20

GAD T one weighted scan.

6:23

This is our A DC map

6:25

and we see some areas in particularly the anterior border

6:28

of this which have dark signal intensity, which is

6:31

darker than gray matter and white matter and

6:34

therefore reduction in a DC, which would lead us

6:38

to the conclusion that this may have a higher grade.

6:42

And if we look at our perfusion map, remember

6:45

that the gray matter, which is the blue,

6:49

is more perfused than white matter, which is the

6:53

aqua green here.

6:54

So this lesion, which is darkish blue,

6:58

has increased perfusion.

7:00

It has perfusion as much as,

7:02

or even more than the gray matter.

7:04

And again, this is all visual assessment.

7:07

Sumi Cha will talk to you

7:08

and if you look up her papers, she has some values

7:11

that they place for CBV and CBF.

7:13

The problem is that there is some variation between them,

7:16

depending upon whether you're using a 1.5 Tesla scanner

7:19

or a three Tesla scanner

7:21

and what parameters you're using

7:23

for your profusion sequence.

7:25

But in this example, I as a visual assessment, this is

7:30

a hyper perfused tumor and

7:32

therefore we would suggest it's more likely

7:33

to be a higher grade astrocytoma.

7:37

This is a grade four tumor.

7:39

Now grade four tumors include glioblastomas,

7:43

but the glioblastomas are not IDH mutant.

7:46

So IDH wildtype grade four tumor glioblastoma,

7:51

IDH mutant grade four tumor is a high grade astrocytoma,

7:56

in this case astrocytoma IDH mutant grade four.

8:00

Now I mentioned molecularly if they have the CD, K

8:05

and two A two B two a B mutation, that's going

8:10

to define grade four

8:12

or if the histopathologically,

8:14

you have microvascular proliferation

8:16

and necrosis on histopathology that will define grade four.

8:21

These are both grade four tumors

8:23

and yet they look pretty well defined once again.

8:26

But this one had that genetic marker

8:29

and this one histopathologically had necrosis.

8:31

But in general, once again, the higher the grade,

8:36

the lower the A DC values

8:38

and the greater the profusion of the tumor.