Neural Correlates of Ongoing Chronic Low Back Pain as ...kawin/BrainMap/BrainMapTalk_Marco.pdf ·...
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Marco L. Loggia, PhD Neural Correlates of Neural Correlates of Ongoing Chronic Low Back Pain Ongoing Chronic Low Back Pain as Measured by as Measured by Arterial Spin Labeling (ASL) Arterial Spin Labeling (ASL) http://diseases-blog.blogspot.com
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Transcript of Neural Correlates of Ongoing Chronic Low Back Pain as ...kawin/BrainMap/BrainMapTalk_Marco.pdf ·...
Ma
rco
L. L
og
gia
, P
hD
Ne
ura
l C
orr
ela
tes
of
Ne
ura
l C
orr
ela
tes
of
On
go
ing
Ch
ron
ic L
ow
Ba
ck
Pa
in
On
go
ing
Ch
ron
ic L
ow
Ba
ck
Pa
in
as
Me
as
ure
d b
y
as
Me
as
ure
d b
y
Art
eri
al S
pin
La
be
lin
g (
AS
L)
Art
eri
al S
pin
La
be
lin
g (
AS
L)
htt
p:/
/dis
eases-b
log.b
logspot.
com
Outlin
e o
f th
e talk
•C
hro
nic
Lo
w B
ack P
ain
•Im
ag
ing
th
e b
rain
in
pa
in
•In
tro
to
Art
eri
al S
pin
La
be
ling
•S
tud
yin
g C
LB
P w
ith
AS
L
•C
on
clu
sio
ns
Chro
nic
Low
Back P
ain
•L
ow
ba
ck p
ain
is the
fif
th m
os
t c
om
mo
n r
ea
so
nfo
r a
ll p
hysic
ian
vis
its in
th
e U
SA
an
d a
le
ad
ing
ca
use
of d
isa
bili
ty
•T
he
pro
po
rtio
n o
f pe
op
le w
ho
se
lf-r
ep
ort
to
ha
ve lo
w b
ack p
ain
th
at
inte
rfe
res w
ith
th
eir d
aily
fu
nction
ing
is ~
25
%
•in
85
%o
f th
e in
div
idu
als
rep
ort
ing
back p
ain
, n
o d
efinitiv
e d
iag
no
sis
ca
n b
e m
ade
(C
avan
au
gh
an
d W
ein
ste
in, 1
99
4; D
eyo
, 1
99
8)
Chro
nic
Low
Back P
ain
•E
ve
n w
he
n a
na
tom
ic a
bn
orm
alit
ies a
re d
ete
cte
d, th
e s
ign
ific
ance
is
un
cle
ar
�T
he
id
en
tifica
tio
n o
f b
iom
ark
ers
fo
r C
LB
P w
ou
ld h
ave
sig
nific
ant
clin
ica
l im
plic
atio
ns.
L5
-S1
dis
c p
rotr
usio
n in
a 2
4-y
.o.
wo
ma
n w
ith
no
ba
ck p
ain
Jen
sen
et
al.,
Ne
w E
nglJ M
ed
, 1994
Why lookin
g into
the b
rain
?•
Mo
st o
f th
e r
ese
arc
h o
n c
hro
nic
pa
in to
da
te is a
t th
e s
pin
al cord
le
ve
l
•B
ut…
str
uctu
ral a
nd
ne
uro
ch
em
ica
lch
ang
es h
ave
be
en
re
port
ed
in
p
ain
pa
tie
nts
Ap
ka
ria
ne
t a
l.,
JN
eu
rosci20
04
Sem
ino
wic
z e
t a
l.,
Ga
str
oen
tero
l20
10
str
uc
tura
l c
ha
ng
es
in
LB
Ps
tru
ctu
ral
ch
an
ge
s i
n I
BS
ne
uro
ch
em
ica
lc
ha
ng
es
in
Fib
rom
ya
lgia
Ha
rris
et a
l.,
Art
hritis R
he
um
at
2009
See
als
o K
uch
inad
et a
l.,
JN
eu
rosci2
007
; D
aS
ilva
et
al.,
PLo
S2008
, e
tc
Imagin
g b
rain
responses to p
ain
Ap
ka
ria
ne
t a
l 2
00
5
Imagin
g b
rain
responses to p
ain
Th
is typ
e o
f de
sig
n h
igh
ligh
ted
the
occurr
en
ce
of a
ug
me
nte
d
ce
ntr
al p
ain
pro
ce
ssin
gin
pa
tie
nts
with
chro
nic
pa
in.
Fo
r in
sta
nce, th
e a
pp
lica
tion
of th
e s
am
e s
tim
ulu
s to L
BP
or
FM
w
as a
ssocia
ted
with
str
ong
er
an
d m
ore
exte
nd
ed
activa
tio
ns th
an
in
HC
(e
.g., G
iese
cke
et a
l., A
rthri
tis R
heu
m, 20
04)
Bu
t h
ow
ca
n w
e s
tud
y C
LIN
ICA
L p
ain
?
Imagin
g b
rain
responses to p
ain
Fro
m e
xperi
menta
l to
clin
ical pa
in
•M
ost o
f e
xp
erim
en
tal p
ain
is b
rie
f/cu
tan
eo
us, w
here
as c
linic
al p
ain
(C
P)
is d
ee
p a
nd
pro
lon
ged
.
•F
urt
herm
ore
, n
orm
ally
CP
ca
nn
ot be
sw
itch
ed
on a
nd
(esp
ecia
lly)
off a
t w
ill
�C
P te
nds to
elu
de
stu
dy w
ith
blo
ck o
r e
ve
nt-
rela
ted
exp
eri
me
nta
l p
ara
dig
ms a
nd
BO
LD
im
agin
g
Ap
ka
ria
ne
t a
l.,
Neu
rosciLe
tte
rs,
2001
Tim
e
Online pain rating
Altern
ative a
ppro
aches t
o
the ‘tw
o-s
tate
subtr
action’desig
ns
•C
orr
ela
tin
g the
on
line
tem
po
ral pro
file
of p
ain
with
BO
LD
sig
na
l
Ba
liki, J
Neu
rosci2006
•R
estin
g s
tate
co
nne
ctivity a
na
lyse
s Napa
do
w e
t al.,
Art
hritis
Rh
eum
2010
Altern
ative a
ppro
aches t
o
the ‘tw
o-s
tate
subtr
action’desig
ns
Anoth
er
alte
rnative
:
‘tw
o-s
tate
subtr
action’de
sig
n
with A
rterial S
pin
Labelin
g (
AS
L)
Art
eria
l spin
labelin
g
•A
rte
ria
l spin
la
belin
g (
AS
L)
is a
fa
mil
yo
f M
RI
tech
niq
ue
s w
hic
h u
se w
ate
r in
art
eri
al
blo
od
as a
fre
ely
diffu
sib
le t
race
r to
me
asu
re p
erf
usio
n n
onin
va
siv
ely
.
•A
rte
ria
l blo
od
is t
ag
ge
d b
y s
atu
ratin
g/in
ve
rtin
g t
he
lo
ng
itu
din
al co
mpo
ne
nt
of
the
MR
sig
nal
•O
nce
in
th
e c
ap
illa
rie
s,
the
ta
gg
ed
wa
ter
pa
sse
s in
to t
he
bra
in t
issu
e,
wh
ere
it
alte
rs
the
lo
ca
l tissu
e’s
lo
ngitu
din
al m
ag
ne
tiza
tio
n
•In
terl
ea
ve
d w
ith
th
e ‘ta
g im
ag
es’are
usu
ally
‘co
ntr
ol im
ag
es’, in
wh
ich
th
e
ma
gn
etiza
tio
n o
f a
rte
ria
l b
loo
d is f
ully
re
laxe
d % signal change
from previous volume
Tag
im
ag
es
Tim
e
Co
ntr
ol im
ag
es
Art
eria
l spin
labelin
g
•O
f th
e s
equences a
vaila
ble
at
MG
H,
the S
iem
ens-
support
ed s
eq
uence is e
p2d
_p
asl,
a P
ICO
RE
-Q2T
IPS
seque
nce
•‘T
ag’im
ages a
re a
cquir
ed b
y labe
ling a
thic
k invers
ion s
lab
(~10cm
), p
roxim
al to
the im
agin
g s
lices;
‘Co
ntr
ol’
ima
ges
are
acqu
ired b
y a
pply
ing a
n o
ff-r
esonance in
vers
ion p
uls
e
without
an
y s
patial encodin
g g
radie
nt.
Lu
he
t a
l.,
Ma
gn
Re
son
Med
, 1999
•S
ubtr
action o
f th
e lab
ele
d (
“tag”)
im
age f
rom
a r
efe
rence (
“contr
ol”)
ima
ge
pro
duces a
perf
usio
n-w
eig
hte
d im
age,
wh
ich
is p
roport
ionalto
CB
F
Liu
and
Bro
wn
, J I
nt
Neu
rop
sych
So
c 2
007
Art
eria
l spin
labelin
g
•T
he p
erf
usio
n-w
eig
hte
d im
ag
es c
an b
e f
urt
her
pro
cesse
d t
o o
bta
in
quantita
tive
CB
F m
ap,
in a
bso
lute
units (
in m
l/100g/m
in)
rCB
Fm
ap
(m
l/100g
r o
f ti
ssu
e/m
in)
Equa
tio
n f
rom
JJ-W
ang e
t a
l. J
MR
I 18
:404
-413
, 2003
*
Art
eria
l spin
labelin
g
•C
ross-v
alid
ation s
tudie
s,
and c
linic
al ap
plic
ations
Ye
et
al.,
Ma
gn
Re
son
Me
d, 20
00
Hyp
op
erf
usio
nin
an
acu
te s
tro
ke
Hyp
erp
erf
usio
nin
a g
lyo
bla
sto
ma
Joh
n D
etr
e,
MA
GN
ET
OM
Fla
sh
2008
H2
150 P
ET
AS
L
J C
he
n,
Int
J B
iom
ed
Ima
g, 20
08
Art
eria
l spin
labelin
g
•A
lth
ou
gh
CP
ca
nn
ot be
easily
tu
rned
off a
t w
ill, it is p
ossib
le to
in
cre
ase
it b
y o
pp
ort
un
e m
an
ipu
latio
ns.
•W
e h
ypo
thesiz
ed
th
at:
–A
n in
cre
ase
in
on
go
ing
pa
in w
ill b
e a
ssocia
ted
with
an in
cre
ase
in
rC
BF
in b
rain
are
as in
vo
lve
d in
ce
ntr
al p
ain
pro
cessin
g
–A
s A
SL
allo
ws the
qua
ntifica
tio
n o
f C
BF
, th
is te
ch
niq
ue
will
allo
w
to d
ete
ct th
ese
cha
nge
s.
Rationale
of th
e s
tudy
Part
icip
ants
•16 p
atie
nts
suffering f
rom
dis
cog
en
iclo
w b
ack a
nd
radic
ula
rpain
for
more
than s
ix m
onth
s.
•16 a
ge-
an
d g
end
er-
matc
hed h
ea
lthy c
ontr
ols 1
3.1
4154
43.2
5C
ontr
ol
M
15.4
3373
44.2
5P
atient
M
12.0
7552
48.2
7273
11
Contr
ol
F
13.5
794
49
11
Patient
F
Ag
e S
tDev
Ag
e m
ean
NP
ati
en
t/ctr
lG
en
der
Pro
cedure
s
©bpac
nz(2
01
0)
Pa
tien
ts –
Clin
ica
l m
aneu
ve
rs
Con
tro
ls –
Clin
ica
l m
ane
uve
rs
Pa
tien
ts –
Hea
t pa
in
Ima
gin
g a
cqu
isitio
n a
nd a
naly
ses
•6 m
inute
sp
uls
ed
AS
Lscans w
ere
colle
cte
d u
sin
g t
he “
PIC
OR
E-Q
2T
IPS
”M
RI
labelin
g m
eth
od w
ith a
3 T
Sie
mens T
IM T
rio M
RI
Syste
m,
equip
ped
with a
32-c
han
nel he
ad c
oil
(TR
/TE
/TI1
/TI2
= 3
000/1
3/7
00/1
700m
s;
Thic
kness o
f la
belin
g r
eg
ion =
110m
m,
Gap=
21.1
mm
).
•V
oxelsiz
e:
3.5
x3.5
x6.2
5;
16 s
lices
•C
ontr
ol a
nd T
ag im
ages w
ere
motion c
orr
ecte
d,
surr
oun
d s
ubtr
acte
d a
nd
then f
urt
her
pro
cessed t
o o
bta
in q
uantita
tive
CB
F m
aps.
•C
BF
maps w
ere
inte
rpo
late
d o
nto
Fre
esurf
er-
reconstr
ucte
d s
urf
aces,
and
then s
mooth
ed
with a
kern
el o
f ~
7m
m (
2*v
oxelsiz
e)
•C
han
ges in C
BF
were
com
pute
d f
or
each s
ubje
ct,
inte
rpo
late
d o
nto
sta
ndard
sp
ace (
fsavera
ge)
and t
hen g
roup-a
vera
ged
•M
onte
carl
osim
ula
tio
ns r
un t
o c
orr
ect
for
multip
le c
om
pariso
ns (
vert
ex
thre
shold
of
p=
0.0
1)
Results
Cli
nic
al
man
eu
ve
rs w
ere
pain
ful fo
r p
ati
en
ts,
bu
t n
ot
for
the c
on
tro
ls.
No
xio
us h
eat
eli
cit
ed
rati
ng
s w
hic
h a
pp
roxim
ate
d t
he p
ain
se
ve
rity
evo
ked
by
cli
nic
al
man
eu
ve
rs.
In p
ati
en
ts, clin
ical
man
eu
vers
, b
ut
no
t h
eat,
in
du
ced
a c
lin
icall
y s
ign
ific
an
t
incre
ase i
n o
ng
oin
g p
ain
(>
30
%)
pe
rch
clb
ple
gse
s1
0
15
20
25
30
35
40
45
Aft
er
he
at
Aft
er
man
eu
vers
% change in ongoing pain
Clin
ica
lly s
ign
ific
an
t pa
in in
cre
ase
N surface vertices
rCB
F(m
l/100g
r tissue/m
in)
Es
tim
ate
d a
ve
rag
e C
BF
yie
lde
d p
hys
iolo
gic
all
y p
lau
sib
le v
alu
es
No
CB
F d
iffe
ren
ces
were
ob
se
rve
d b
etw
ee
n p
ati
en
ts a
nd
co
ntr
ols
at
ba
se
lin
e
Results
Ye
et
al., 20
00
Aft
er
the
(p
ain
les
s)
clin
ica
l m
an
eu
ve
rs, c
on
tro
ls d
id n
ot
ex
hib
it a
ny
inc
reas
e in
th
e r
CB
F
Results
Con
tro
ls –
Clin
ica
l m
ane
uve
rs
Sim
ila
rly, a
fte
r th
e h
ea
t p
ain
(w
hic
h d
id n
ot
ca
us
e a
clin
ica
lly
sig
nif
ica
nt
inc
reas
e in
pa
in)
pa
tie
nts
did
no
t ex
hib
it a
ny in
cre
as
e in
th
e r
CB
F
Results
Pa
tien
ts –
Hea
t pa
in
Results
Pa
tien
ts –
Clin
ica
l m
aneu
ve
rs
Ho
we
ve
r, a
fte
r th
e p
ain
-wo
rse
nin
g c
lin
ica
l m
an
eu
ve
rs, p
ati
en
ts
ex
hib
ite
d r
CB
Fin
cre
as
es
, o
ve
r a
wid
es
pre
ad
netw
ork
of
are
as
Results
Th
es
e a
rea
s in
clu
de
d:
Pri
ma
ry a
nd
se
co
nd
ary
so
ma
tose
ns
ory
co
rtic
es. A
mo
ng
th
e
str
uctu
res m
ost co
mm
on
ly a
ctiva
ted in
pa
in im
ag
ing
stu
die
s, are
tho
ug
ht
to e
nco
de
the s
ensory
co
mp
on
ents
of pain
.
S1
active
at th
e le
ve
l o
f th
e p
ara
ce
ntr
allo
bu
le (
se
nsori
mo
tor
repre
sen
tation
of th
e le
g)
S1 S2
Results
Rig
ht
an
teri
or
ins
ula
. A
no
ther
very
com
mon
ly a
ctiva
ted
reg
ion
in p
ain
stu
die
s, b
elie
ve
d to
be
in
vo
lve
d in
en
cod
ing
se
nsory
an
d/o
r a
ffective
co
mp
one
nts
of p
ain
, a
s w
ell
as in
in
tero
cep
tio
n.
An
teri
or
Insu
la
Results
Bo
th in
su
laa
nd
S2
ha
ve
be
en
im
plic
ate
d in
id
iop
ath
ic p
ain
co
nd
itio
ns,
such
as fib
rom
ya
lgia
.
Napa
do
w e
t al.,
Art
hritis
Rh
eum
2010
Results
Do
rso
late
ralp
refr
on
tal c
ort
ex
. R
eg
ion
wh
ich
ha
ve
be
en
fo
un
d to
be
h
yp
otr
op
hic
in p
atie
nts
with
chro
nic
lo
w b
ack p
ain
(A
pkari
an
et a
l., 2
00
6)
DL
PF
C
Ap
ka
ria
ne
t a
l.,
JN
eu
rosci20
04
Results
Me
dia
l p
refr
on
tal c
ort
ex
. A
reas w
hic
h h
ave
bee
n im
plic
ate
d in
both
lo
w
ba
ck p
ain
(B
alik
ie
t a
l., 2
006
) a
s w
ell
as in
rh
eum
ato
id a
rth
ritis
(Sch
we
inh
ard
te
t a
l., 2
00
8)
MP
FC
Ba
likie
t a
l.,
JN
eu
rosci20
06
Rheu
ma
toid
art
hritis
Sch
we
inha
rdte
t a
l.,
Neu
roim
age
20
08
Results
Su
pe
rio
r p
ari
eta
l lo
bu
le. Im
plic
ate
d in
atte
ntio
na
l m
echa
nis
ms, an
d n
ot
ve
ry o
fte
n s
ee
n a
ctive
in
pa
in s
tud
ies. H
eig
hte
ne
d v
igila
nce
to
clin
ica
l sym
pto
ms?
SP
L
Th
e a
vera
ge
rC
BF
incre
ase
cau
se
d b
y th
e c
linic
al m
an
eu
vers
was
~6m
l/1
00
gr
tis
su
e/m
in
Results
pc
gro
up
-15
-10-505
10
15
20
25
L paracentral
pc
gro
up
-8-6-4-202468
10
12
14
16
18
20
22
L rostral middle frontal
pc
gro
up
-10-505
10
15
20
25
30
R supramarg
pc
gro
up
-20
-100
10
20
30
40
R postcentr
pc
gro
up
-15
-10-505
10
15
20
25
30
35
R paracentral
pc
gro
up
-15
-10-505
10
15
20
25
30
R sup frontal
De
lta C
BF
aft
er
clin
ica
l m
aneuvers
: R
aw
va
lues
Conclu
sio
ns
•E
xa
ce
rba
tio
n o
f clin
ica
l p
ain
is a
sso
cia
ted
with
the
CB
F in
cre
ase
in
a
wid
esp
rea
d n
etw
ork
of are
as, in
clu
din
g a
reas o
f th
e ‘e
vo
ked
pa
in
ma
trix
’(a
nte
rio
r in
su
la, S
1, S
2),
an
d r
eg
ion
s less c
om
mo
nly
see
n
active
in
exp
eri
me
nta
l p
ain
stu
die
s (
e.g
., S
PL
)
•T
he
se fin
din
gs furt
her
su
ppo
rt th
e n
otio
n th
at chro
nic
pa
in s
tate
s
affect ce
ntr
al p
ain
pro
cessin
g
•A
SL
is a
pro
mis
ing
too
l to
in
ve
stig
ate
th
e n
eu
ral p
rocessin
g o
f C
P,
an
d p
rovid
es a
ste
p fo
rward
in
th
e q
uest fo
r o
bje
ctive
bio
mark
ers
of
CP
.
•M
ore
in
ge
nera
l, A
SL
ap
pea
rs to b
e a
use
ful com
ple
me
nt to
BO
LD
fM
RI im
ag
ing in
th
e s
tud
y o
f bra
in fun
ctio
n, as it ca
n b
e s
uccessfu
lly
ap
plie
d in
desig
ns in
wh
ich
BO
LD
is s
ub
op
tim
al
Thanks to…
•A
jay W
asa
n
•R
an
dy G
ollu
b
•L
i C
he
n
•Je
an
Ch
en
•V
ita
ly N
ap
ad
ow
•D
iv B
ola
r
•D
ou
g G
reve
•Jia
n K
on
g
•G
art
h C
oo
mb
s
Thanks to…
.
