F R O M THE D E P A R T M E N T O F N E U R O L O G Y , S O D E R S J U K H U S E T , S-100 64 S T O C K H O L M , S W E D E N .
QUANTITATIVE CISTERNOGRAPHY U.
In 1953 the use of
1 3 1
LYING-TUNELL
I - H S A o r R I S A w a s i n t r o d u c e d for s c i n t i m y e l o g r a p h y ( B A U E R
& Y U H L 1953). T h e C S F turnover of R I S A w a s e x p e r i m e n t a l l y a n a l y s e d by ISHIBASHI (1959). In m a n , a n e x p o n e n t i a l d i s a p p e a r a n c e of R I S A f r o m C S F has b e e n f o u n d f o l l o w i n g direct injection i n t o the cerebral ventricles, e m p l o y i n g either serial s a m p l i n g of C S F ( A T K I N S O N & F O L T Z 1962) o r external d e t e c t i o n ( M U N D I N G E R et coll. 1963). D i C H I R O (1964) i n t r o d u c e d R I S A c i s t e r n o g r a p h y for e v a l u a t i o n of the m o v e m e n t of C S F after l u m b a r injection of t h e tracer a n d external s c a n n i n g of t h e h e a d . T h i s m e t h o d w a s quantified ( L Y I N G - T U N E L L et coll. 1970), a n d later d e v e l o p e d u s i n g dif ferent external d e t e c t o r devices ( L Y I N G - T U N E L L & S O D E R B O R G 1 9 7 2 a, b ) .
Methods Primarily, a w h o l e - b o d y scanner w a s u s e d , w i t h a f o c u s s e d c o l l i m a t o r a n d a regional d o t c o u n t i n g t e c h n i q u e a p p l i e d t o the scintigrams ( L Y I N G - T U N E L L & S O D E R BORG 1972 a). T h i s m e t h o d h a d certain d i s a d v a n t a g e s a n d a stationary
detector
system w i t h a l o n g straight b o r e lead c o l l i m a t o r w a s c o n s t r u c t e d . T h e d e s i g n a n d i s o response curves of t h e c o l l i m a t o r , as well as its p o s i t i o n i n g i n relation t o t h e basal cisterns have b e e n described p r e v i o u s l y
(LYING-TUNELL
& SODERBORG
1972 b ,
SODERBORG & L Y I N G - T U N E L L 1973). After l u m b a r injection of 3 7 0 0 k B q ( 1 0 0 /uCi) 1 3 1
I - H S A m e a s u r e m e n t s w e r e p e r f o r m e d f r o m t h e b a s a l cisterns a n d t h e parasagittal
region in anterior projections (Fig. 1) a n d f r o m the left u p p e r arm. T h e d i s a p p e a r a n c e of the tracer f r o m the basal cisterns w a s e x p o n e n t i a l a n d t h u s a b i o l o g i c half t i m e The author is now at Department of Neurology, Huddinge Sjukhus, S-141 86 Huddinge. Sub mitted for publication 23 December 1977. Acta Radiologica Diagnosis 19 (1978) Fasc. 6
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905
906
U. LYING-TUNELL CPM 2000-)
Fig. 1. Measurements from bas al cisterns ( O ) and parasagittal region ( • ) in one patient after subarachnoid injection of IHSA. 131
Hours
( B H T ) of the clearance c o u l d be calculated (Fig. 2 ) . Curves recorded f r o m the parasagittal region were often m o r e irregular. Tissue
background.
C a l c u l a t i o n s were b a s e d o n m e a s u r e m e n t s w i t h the stationary
d e t e c t o r f r o m t h e basal cisterns after i n t r a v e n o u s and s u b a r a c h n o i d
injections,
respectively ( L Y I N G - T U N E L L & S O D E R B O R G 1 9 7 2 b). After i n t r a v e n o u s injection, the q u o t i e n t of basal cistern t o arm activity w a s fairly c o n s t a n t , a n d t h u s it w a s possible t o calculate a p p r o x i m a t e l y the m a g n i t u d e of the c o n t r i b u t i o n of tissue b a c k g r o u n d at different times. A s s u m i n g that o n e w e e k after s u b a r a c h n o i d injection m o s t of the tracer h a s left t h e C S F , w h i c h is t h e n in equilibrium w i t h o t h e r tissues, the ratio of basal cistern t o a r m activity w a s calculated o n e w e e k after s u b a r a c h n o i d injection for cisternography. W i t h the c o r r e c t i o n factor t h u s o b t a i n e d , repeat m e a s u r e m e n t s of c o u n t rates o v e r the a r m were used t o calculate t h e tissue b a c k g r o u n d in the region of t h e basal cisterns at different times. T h e B H T w a s a l w a y s shorter after correction for tissue b a c k g r o u n d , t h e c o n t r i b u t i o n of w h i c h o b v i o u s l y increases with time. T h e level of tissue b a c k g r o u n d w a s f o u n d t o vary c o n s i d e r a b l y b e t w e e n different e x a m i n a t i o n s , intraindividually as well as interindividually. T h e m e t h o d , i n c l u d i n g corrections for i s o t o p e d e c a y a n d for r o o m and tissue b a c k g r o u n d , w a s a p p l i e d p r o s p e c t i v e l y in a series of 7 0 patients e x a m i n e d with i s o t o p e c i s t e r n o g r a p h y ( L Y I N G - T U N E L L 1 9 7 7 ) . T h e n o m e n c l a t u r e for tracer kinetics suggested b y B R O W N E L L et coll. ( 1 9 6 8 ) w a s used. E a c h p o i n t o n the curves w a s w e i g h t e d with regard t o t h e total error, m a i n l y d e p e n d e n t o n c o u n t i n g statistics. H o w e v e r , the dif ferences b e t w e e n w e i g h t e d a n d n o n - w e i g h t e d v a l u e s were small and did n o t signif icantly influence t h e B H T c a l c u l a t i o n s . T h e error in d e t e r m i n i n g these
separate
p o i n t s , e s t i m a t e d b y r e p e a t i n g the m e a s u r e m e n t s in the s a m e patients within 3 0 min
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907
QUANTITATIVE CISTERNOGRAPHY CPM
hours
hours
Fig. 2. Representative semilog curves from 2 patients measured over the basal cisterns.
after r e p o s i t i o n i n g the d e t e c t o r , w a s f o u n d t o b e 3 . 8 per c e n t (n = 6 7 pairs). T h e straight lines o b t a i n e d in s e m i l o g a r i t h m i c p l o t s derived f r o m m e a s u r e m e n t s after p e a k activity h a d b e e n reached, viz. after 1 6 u p t o 4 8 h f o l l o w i n g injection. T h e y h a d h i g h correlation coefficients, with r - v a l u e s > 0 . 9 9 in 6 4 of t h e 7 0 cases. T h e error in deter m i n i n g the individual B H T , c a l c u l a t e d as t h e m e d i a n of t h e s t a n d a r d d e v i a t i o n s in the 7 0 curves, w a s f o u n d t o be 5 per c e n t of the m e a n B H T . C o r r e c t i o n for tissue b a c k g r o u n d in t h e s e 7 0 cases c a u s e d a n average decrease of B H T of 2 0 per c e n t (SE
2 % , range 0 - 6 9 % ) .
Reproducibility.
D u r i n g several years q u a n t i t a t i v e c i s t e r n o g r a p h y w a s p e r f o r m e d
twice in a n u m b e r of patients, usually b e c a u s e at t h e first a t t e m p t t h e a m o u n t of activity reaching the skull w a s insufficient for scintigraphy, t h o u g h it w a s e n o u g h for q u a n t i t a t i v e m e a s u r e m e n t s w i t h t h e s t a t i o n a r y d e t e c t o r . P a t i e n t s w i t h a m a j o r head injury or a n y o t h e r incident w h i c h c o u l d p o s s i b l y h a v e affected the C S F s y s t e m b e t w e e n the 2 e x a m i n a t i o n s were e x c l u d e d . F o u r t e e n p a t i e n t s w i t h repeat c i s t e r n o g r a p h y r e m a i n e d for e v a l u a t i o n of the r e p r o d u c i b i l i t y of the m e t h o d ; 7 w i t h d e m e n t i a . T h e interval b e t w e e n t h e 2 c i s t e r n o g r a p h i e s r a n g e d f r o m o n e t o 9 m o n t h s . T h e individual B H T values are g i v e n in F i g . 3 . T h e relative error of this m e t h o d of deter m i n i n g cisternographic B H T w a s c a l c u l a t e d t o be 1 1 per cent.
Clinical aspects Biologic
half
time
of basal
cistern
clearance.
In the series of 7 0 p a t i e n t s i s o t o p e
cisternography and encephalography were performed ( L Y I N G - T U N E L L
1977).
The
d e g r e e of d e m e n t i a w a s b a s e d o n n e u r o l o g i c a n d p s y c h o m e t r i c e x p l o r a t i o n ( L Y I N G T U N E L L & M A R I O N S 1 9 7 5 b). T h e d i s a p p e a r a n c e rate of the tracer f r o m t h e basal cisterns w a s significantly s l o w e r in p a t i e n t s w i t h d e m e n t i a of different origins t h a n in the subjects w i t h o u t o b v i o u s brain injury, i.e. the B H T w a s significantly l o n g e r ( p < 0 . 0 0 1 ) in t h e patients w i t h d e m e n t i a ( F i g . 4 a), e v e n w h e n c o n s i d e r i n g s e p a r a t e l y
Downloaded from acr.sagepub.com at University of Manitoba Libraries on June 25, 2015
908
U. LYING-TUNELL
Hours
4(h
Fig. 3. Biologic half time from 14 patients having undergone 2 cisternographies (I and II); r = 0.97, p < 0.001, (with the point in the upper right corner excluded, r = 0.83, p < 0.001).
'"
•
/ /
/ / V_
]
10
20
30 I
40 Hours
t h o s e w i t h o n l y slight m e n t a l r e d u c t i o n . T h e 1 7 p r e s u m a b l y n o r m a l subjects h a d a m e a n B H T of 9 . 8 h ( S D 4 . 1 ) . T h e v a l u e s in this g r o u p were fairly well separated f r o m t h o s e w i t h m a r k e d d e m e n t i a , 1 2 h c o n s t i t u t i n g a borderline v a l u e . A t e n c e p h a l o g r a p h y , t h e B H T v a l u e s correlated best w i t h t h e presence of biparietal convexity
air
block
(LYING-TUNELL &
MARIONS
1 9 7 5 a,
b,
MARIONS
&
LYING-
T U N E L L 1 9 7 7 ) , E v a n ' s i n d e x a n d t h e transversal w i d t h of t h e p o s t e r i o r part of t h e third ventricle. T h e c o m b i n e d results f r o m e n c e p h a l o g r a p h y a n d quantitative i s o t o p e c i s t e r n o g r a p h y h a d t h e best discriminative p o w e r in that all p a t i e n t s w i t h m e n t a l r e d u c t i o n of a n y degree h a d B H T > 1 2 h, o r parietal air b l o c k , o r b o t h . E n c e p h a l o g r a p h y is n o w t o s o m e e x t e n t replaced b y c o m p u t e r t o m o g r a p h y ( C T ) ; G A D O e t coll. ( 1 9 7 6 ) f o u n d a c l o s e c o r r e l a t i o n b e t w e e n C T findings a n d t h o s e at isotope cisternography in dementia. Normal
pressure
hydrocephalus
and effect
of CSF shunting.
F o u r patients with
n o r m a l pressure h y d r o c e p h a l u s a c c o r d i n g t o classic criteria ( O J E M A N N et coll. 1 9 6 9 ) w e r e e x a m i n e d b y q u a n t i t a t i v e c i s t e r n o g r a p h y b e f o r e a n d after clinically successful ventriculo-atrial s h u n t i n g a d m o d u m P u d e n z u s i n g a l o w pressure valve. O n e of t h e s e p a t i e n t s h a d a h i s t o r y of s u b a r a c h n o i d h e m o r r h a g e a n d a d u r a t i o n of s y m p t o m s of 3 m o n t h s , o n e a h i s t o r y of s t e r e o t a c t i c cerebral surgery f o r p a r k i n s o n i s m a n d a duration of s y m p t o m s for 2 1 months; in the remaining 2 patients n o etiology w a s k n o w n a n d t h e d u r a t i o n of s y m p t o m s w a s 6 years. O b s e r v a t i o n t i m e after s h u n t i n g r a n g e d b e t w e e n 2 . 5 a n d 4 y e a r s . A l l i m p r o v e d c o n s i d e r a b l y . O n e of t h e p a t i e n t s w i t h i d i o p a t h i c h y d r o c e p h a l u s , a 6 6 - y e a r - o l d w o m a n , h a d a clinical history of p r o g r e s s i v e d e t e r i o r a t i o n f o r 6 years. S h e w a s disoriented w i t h a K o r s a k o f f defect
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QUANTITATIVE CISTERNOGRAPHY
909
of m e m o r y , u n a b l e t o walk, s t a n d o r e v e n sit b y herself, a n d w a s i n c o n t i n e n t . A n excellent, a l t h o u g h s o m e w h a t u n e x p e c t e d , clinical i m p r o v e m e n t e n s u e d a s h u n t i n g p r o c e d u r e ; she b e c a m e c o n t i n e n t , able t o w a l k w i t h o u t a n y difficulty a n d w a s dis c h a r g e d f r o m the h o s p i t a l in a n i m p r o v e d m e n t a l state, a slight m e m o r y d i s o r d e r being the o n l y residue. T h e o b s e r v a t i o n t i m e w a s 4 years. T h e patient w i t h s u b a r a c h n o i d h e m o r r h a g e h a d a similar c o u r s e of
excellent
i m p r o v e m e n t . T h e r e m a i n i n g 2 patients a l s o i m p r o v e d c o n s i d e r a b l y after s h u n t i n g . E n c e p h a l o g r a p h y and i s o t o p e c i s t e r n o g r a p h y w e r e p e r f o r m e d in all p a t i e n t s ; b e fore s h u n t i n g all h a d a m a r k e d c o m m u n i c a t i n g h y d r o c e p h a l u s , persistent ventricular i s o t o p e activity and a c o n v e x i t y b l o c k for b o t h air a n d i s o t o p e s . T h e w a s h o u t of R I S A f r o m the b a s a l cisterns w a s c a l c u l a t e d u s i n g t h e c o r r e c t i o n for tissue b a c k g r o u n d ; the B H T v a l u e s a p p e a r in F i g . 4 b. Before s h u n t i n g , the w a s h o u t w a s s l o w ; after shunting t h e B H T v a l u e s were all shorter a n d fell well w i t h i n t h e p o s t u l a t e d n o r m a l range. P o s t o p e r a t i v e i s o t o p e c i s t e r n o g r a p h y indicated f l o w of activity t o t h e ventricles after 2 4 h, m o r e or less persistent a l s o after 4 8 h. N o a p p a r e n t activity w a s r e c o r d e d in t h e Sylvian or interhemispheric fissures, n o r o v e r t h e c o n v e x i t y , e x c e p t p o s s i b l y in o n e case. In 2 p a t i e n t s , c i s t e r n o g r a p h y u s i n g different i s o t o p e s w a s p e r f o r m e d several years after s h u n t i n g (Figs 5, 6). T h e p a t i e n t s were t h e n still in t h e s a m e g o o d clinical c o n d i t i o n s , w i t h f u n c t i o n i n g s h u n t s a n d w i t h scintigraphic i n d i c a tion of a reversed f l o w . It is of interest t o c o m p a r e these results w i t h t h o s e p r e v i o u s l y o b t a i n e d b y t h e
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U. LYING-TUNELL
a
b
c
Fig. 5. Cisternography using T c - H S A 3.5 years after shunting. Anterior views after a) 5, b) 24 and c) 48 hours. Activity in the ventricles and Sylvian fissures even after 48 h in spite of the short physical half time of the isotope used. 9t
m
s c i n t i g r a p h i c m e t h o d f o r q u a n t i t a t i v e c i s t e r n o g r a p h y ( L Y I N G - T U N E L L & SODERBORG 1972 a ) a n d a r e g i o n a l d o t c o u n t i n g t e c h n i q u e ( L Y I N G - T U N E L L & SODERBORG 1972 c), t h o u g h this m e t h o d was a d m i t t e d l y s o m e w h a t crude. At that time, ventriculo-atrial s h u n t s w e r e i n s e r t e d in 6 p a t i e n t s w i t h p r e s e n i l e d e m e n t i a b u t n o gait d i s t u r b a n c e o r urinary
incontinence.
These
patients
had
cisternographic
and
encephalographic
f i n d i n g s c o n s i s t e n t w i t h c e r e b r a l a t r o p h y a c c o r d i n g t o t h e c r i t e r i a given by PATTEN & B E N S O N ( 1 9 6 8 ) . T h e c l e a r a n c e of i s o t o p e f r o m t h e b a s a l c i s t e r n s w a s s l o w . T h e o p e r a t i o n d i d n o t result in a s i g n i f i c a n t clinical i m p r o v e m e n t . Q u a n t i t a t i v e c i s t e r n o g r a p h y w a s c a r r i e d o u t p r e - a n d p o s t o p e r a t i v e l y in 4 of t h e s e p a t i e n t s , r e v e a l i n g n o significant c h a n g e of B H T : p r e o p e r a t i v e l y , t h e m e a n B H T f r o m t h e b a s a l c i s t e r n s w a s 2 2 h ( r a n g e 1 8 - 2 8 h), p o s t o p e r a t i v e l y 23 h ( r a n g e 1 8 - 2 8 h ) .
Discussion I t is e s s e n t i a l t o e v a l u a t e t h e different c o m p a r t m e n t s of t h e C S F s p a c e s e p a r a t e l y in o r d e r t o a v o i d c o m p o s i t e c u r v e s of different m o d e s of flow. T h e c u r v e s f r o m t h e b a s a l c i s t e r n s closely fitted a m o n o - e x p o n e n t i a l f u n c t i o n . T h i s s u p p o r t s t h e a s s u m p t i o n s t h a t o n e c o m p a r t m e n t w a s o b s e r v e d ( S H I P L E Y & C L A R K 1972) w i t h
uniform
d i s t r i b u t i o n of a c t i v i t y a n d n o f u r t h e r inflow of a c t i v i t y i n t o t h e c o m p a r t m e n t u n d e r o b s e r v a t i o n . T h e s e 2 f a c t o r s c o n s t i t u t e p r e r e q u i s i t e s f o r t h e c a l c u l a t i o n of ( S O L O M O N 1949,
L Y I N G - T U N E L L & S O D E R B O R G 1972
BHT
a, S O D E R B O R G & L Y I N G - T U N E L L ) .
In t h e b a s a l c i s t e r n s m a r k e d p u l s a t i v e m o v e m e n t s h a v e b e e n o b s e r v e d ( D u B O U L A Y e t c o l l . 1972), p r o m o t i n g a t h o r o u g h m i x i n g of t h e injected i s o t o p e w i t h C S F in t h i s r e g i o n . P a r t of t h e i n t e r h e m i s p h e r i c fissure p r o j e c t s o v e r t h e b a s a l c i s t e r n s in t h e view u s e d for m e a s u r e m e n t s b u t t h e s e r e g i o n s c o n s t i t u t e a d i r e c t l y c o n t i n u o u s c o m partment. T h e g r e a t v a r i a t i o n in t i s s u e b a c k g r o u n d b e t w e e n different e x a m i n a t i o n s i n d i c a t e s
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QUANTITATIVE CISTERNOGRAPHY
Fig. 6. Cisternography using I n - D T P A 4 years after shunt ing. Anterior and lateral views after a, b) 6, c, d) 24, e, f) 48 and 72 hours, respectively. Activity only in the ventricles as a sign of reversed flow. The shunt valve is demonstrated at 6 and 24 hours. l u
e
f
t h a t it is i m p o r t a n t t o a c c o u n t for t h i s f a c t o r . T h e i n d i c a t o r s u b s t a n c e m a y leave t h e C S F s p a c e a l o n g n e r v e s (STEER & H O R N E Y 1 9 6 8 ) , o r l e a k t o s u r r o u n d i n g
tissues
a t t h e site of injection, c a u s i n g t h e ' h o t s p o t ' w h i c h is often e n c o u n t e r e d . T h u s , t h e m e t h o d of m e a s u r i n g t h e t r a n s p o r t of i s o t o p e s f r o m C S F t o b l o o d , w h i c h h a s b e e n s u g g e s t e d for a s s e s s i n g h y d r o c e p h a l u s ( A B B O T T & A L K S N E 1 9 6 8 ) , is s u b j e c t t o v a r i o u s t e c h n i c a l e r r o r s ( W I L L I A M S e t coll. 1 9 7 0 ) . M A H A L E Y e t coll. ( 1 9 7 4 ) c o m p a r e d n u c l i d e levels in b l o o d a t i s o t o p e c i s t e r n o g r a p h y in 1 5 p a t i e n t s w i t h p r o b a b l e n o r m a l p r e s sure hydrocephalus and 2 2 considered to have Alzheimer's disease. T h e
clinical
c o u r s e of e a c h p a t i e n t w a s f o l l o w e d b y r e v i e w of t h e r e c o r d s . T h e y f o u n d a h i g h e r m e a n b l o o d a c t i v i t y in t h e l a t t e r g r o u p , b u t t h e r e w a s a c o n s i d e r a b l e o v e r l a p in l o w
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v a l u e s b e t w e e n the 2 g r o u p s . T h e a u t h o r s c o n c l u d e d that 7 of t h e 37 patients probably did n o t h a v e n o r m a l pressure h y d r o c e p h a l u s , w h i c h suggests that t h e m e t h o d has a l i m i t e d clinical value. O n l y part of the activity reaches the intracranial C S F space ( D i C H I R O 1966, S O D E R B O R G & L Y I N G - T U N E L L ) b u t the a m o u n t of activity reaching the basal cisterns d o e s n o t influence its clearance ( S O D E R B O R G & L Y I N G - T U N E L L ) . A negligible fraction of t h e i s o t o p e labelled a l b u m i n enters t h e n e r v o u s tissue directly f r o m the C S F (LEE
& O L S Z E W S K I 1960,
H O C H W A L D & W A L L E N S T E I N 1967). M I L H O R A T & H A M M O C K
(1971) c o n s i d e r e d t h e a p p a r e n t d o u b l e o u t l i n e of t h e ventricular system at i s o t o p e v e n t r i c u l o g r a p h y f r o m p a t i e n t s w i t h h y d r o c e p h a l u s as a s u b s t a n t i a t i o n of a rapid a n d extensive m i g r a t i o n of t h e i s o t o p e labelled a l b u m i n i n t o the brain tissue. H o w ever, G R I F F I T H & S T A D D O N ( 1 9 7 3 ) expressed dissentient o p i n i o n s o n the basis of their e x p e r i e n c e u s i n g a glass ventricular m o d e l . In t h e p r e s e n t series, t h e curves f r o m t h e parasagittal region were often m o r e ir regular, p r o b a b l y in part d u e t o t h e relatively late a p p e a r a n c e of m a x i m u m activity, w h e n tissue b a c k g r o u n d h a d r e a c h e d significant levels. M e a s u r e m e n t
geometry
w o u l d a l s o s e e m less suitable: a small shift of the d e t e c t o r u p w a r d s w o u l d result in t h e r e c o r d i n g of v a u l t activity, while a small shift d o w n w a r d s w o u l d result in m e a s u r e m e n t of activity, if any, in the lateral ventricles w i t h a n e x p e c t e d flow dif ferent f r o m t h a t in t h e parasagittal region. M e a s u r e m e n t s o v e r t h e ventricles were a v o i d e d o n a c c o u n t of s u p e r i m p o s i t i o n of the large fissures, i.e. t h e interhemispheric fissure in t h e anterior v i e w , and t h e Sylvian fissures in the lateral view. T h e effect of this is c o n s i d e r a b l e , d u e t o a b s o r p t i o n a n d the inverse square l a w of radiation physics. F o r o b v i o u s r e a s o n s , m e a s u r e m e n t s o v e r t h e entire skull were a v o i d e d . A K E R M A N et coll. ( 1 9 7 2 ) e s t i m a t e d the ventricular v o l u m e f r o m scans and calculated t h e d i s a p p e a r a n c e rate of the tracer f r o m t h e ventricles. H o w e v e r , the m e t h o d has several d i s a d v a n t a g e s , as p o i n t e d o u t b y H A R B E R T e t coll. (1974). Intraventricular i s o t o p e injection is required a n d r e s o l u t i o n is t o o p o o r t o a l l o w a satisfactory defini t i o n of t h e projected ventricular area ( G R I F F I T H & S T A D D O N ) . Certainly a n a n a l o g o u s v o l u m e e s t i m a t e of t h e b a s a l cisterns w o u l d n o t be less crude. T h e m o v e m e n t of i s o t o p e labelled a l b u m i n has b e e n c o n s i d e r e d t o represent 'bulk f l o w ' f r o m the ventricles t o the s u b a r a c h n o i d s p a c e ; the m o d e of m o v e m e n t is clearly d e m o n s t r a t e d at c i s t e r n o g r a p h y ( P E N N I N G & F R O N T 1975). A transient intraventri cular activity d o e s n o t necessarily m e a n that C S F f l o w s b a c k w a r d s . B E L L O N I (1951) d e m o n s t r a t e d by use of a glass m o d e l of t h e C S F s p a c e that pressure variations gave rise t o counter-currents; a s l o w C S F f l o w m a y t h u s b e c o u n t e r a c t e d b y transmitted arterial p u l s a t i o n s . H o w e v e r , t h e patients w i t h n o r m a l pressure h y d r o c e p h a l u s in the present report h a d a m a r k e d , or persistent, ventricular activity. T h i s w a s the case a l s o after insertion of t h e s h u n t t u b e , a l t h o u g h there w a s a c o n c o m i t a n t n o r m a l i z a t i o n of the clearance of i s o t o p e f r o m t h e basal cisterns. T h e s e findings indicate a n increased d r a i n a g e of C S F , m a i n l y t h r o u g h t h e s h u n t t u b e via the ventricles. S u c h scintigraphic i n d i c a t i o n of a reversed f l o w after s h u n t i n g of adult patients agrees
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with other reports ( A L K E R & LESLIE 1 9 6 9 , M A T I N et coll. 1 9 7 0 , M C C U L L O U G H et coll. 1 9 7 2 , C U R L et coll. 1 9 7 2 ) . M C C U L L O U G H e t coll. a n d C U R L e t coll. a l s o f o u n d t h a t total h e a d c o u n t curves h a d a n earlier p e a k a n d a m o r e rapid clearance after s h u n t i n g . F o r m a t i o n a n d a b s o r p t i o n of C S F t a k e s place t h r o u g h o u t t h e s u b a r a c h n o i d s p a c e , w i t h varying rate of e x c h a n g e f o r different c o n s t i t u e n t s ( S W E E T e t coll. 1 9 5 4 ) . T h u s , the turnover of C S F m a y b e increased a l s o b y drainage ' b a c k w a r d s ' . T h e disappear a n c e rate of t h e injected activity is of c o u r s e v o l u m e - d e p e n d e n t ( L Y I N G - T U N E L L & S O D E R B O R G 1 9 7 2 a, S I E G E L & J O H N S O N 1 9 7 4 ) . A p o s t o p e r a t i v e d e c r e a s e i n size of t h e
basal cisterns, if any, w o u l d t h u s c o n t r i b u t e t o a s h o r t e n i n g of t h e B H T f r o m this region. A n increased w a s h o u t of m e t a b o l i t e s f r o m t h e C S F , or, i n t h e case of c h a n g e d surface t o v o l u m e ratio, a n i m p r o v e d e x c h a n g e rate of different s u b s t a n c e s b e t w e e n the brain a n d the C S F , m i g h t i m p r o v e brain m e t a b o l i s m a n d t h u s h a v e bearing u p o n the clinical i m p r o v e m e n t after s h u n t i n g ( L Y I N G - T U N E L L 1 9 7 7 ) . C o n s i s t e n t w i t h this h y p o t h e s i s , a decreased cerebral m e t a b o l i s m w a s f o u n d i n a g r o u p of 7 p a t i e n t s w i t h n o r m a l pressure h y d r o c e p h a l u s , a s c o m p a r e d w i t h 1 0 h e a l t h y subjects, a p p r o a c h i n g n o r m a l levels after clinically successful s h u n t i n g ( L Y I N G - T U N E L L e t coll. 1 9 7 7 ) . A s l o w C S F turnover is c l o s e l y correlated w i t h m e n t a l r e d u c t i o n b u t n o t w i t h a g e p e r se ( L Y I N G - T U N E L L 1 9 7 7 ) . H E N R I K S S O N & V O I G T ( 1 9 7 6 ) r e c e n t l y c l a i m e d t h a t t h e
C S F f l o w n o t o n l y decreases w i t h increasing age, b u t a l s o that this decrease is directly d e p e n d e n t o n age. T h e y e x a m i n e d a series of c i s t e r n o g r a m s w h i c h t h e y regarded a s n o r m a l , b u t the criteria for n o r m a l i t y were d u b i o u s . T h e y d i d n o t report t h e clinical d i a g n o s e s o r mental states of t h e patients. It is well k n o w n that p a t i e n t s w i t h brain a t r o p h y have a t o p o g r a p h i c a l l y n o r m a l distribution of activity o v e r t h e c o n v e x i t i e s at cisternography, a l t h o u g h d e l a y e d ( D E L A N D et coll. 1 9 7 1 ) . It is a l s o well k n o w n t h a t in older a g e g r o u p s d e m e n t i a is p r o b a b l y t h e m o s t i m p o r t a n t i n d i c a t i o n f o r cisternography, with t h e a i m of selecting p a t i e n t s w i t h n o r m a l pressure h y d r o c e p h a l u s w h o m i g h t benefit f r o m shunting. T h u s , a clinically u n s e l e c t e d g r o u p of patients will h a v e cisternographic c h a n g e s c o n c o m i t a n t w i t h a g e , i n t h e s a m e w a y as signs of m y o c a r d i a l infarcts at E C G are m o r e frequent in o l d e r a g e g r o u p s ( L Y I N G T U N E L L 1 9 7 8 ) . T h e signs of a s l o w C S F f l o w , w h i c h H E N R I K S S O N & V O I G T f o u n d i n older a g e g r o u p s , m a y well be a s s o c i a t e d w i t h m e n t a l r e d u c t i o n . A t a n y rate, their results o b v i o u s l y c a n n o t p r o v e the existence of a c a u s a l relationship b e t w e e n c i s t e r n o graphic c h a n g e s a n d a g e p e r se. T h e described m e t h o d of q u a n t i t a t i v e c i s t e r n o g r a p h y h a s theoretical a s w e l l a s clinical implications since it c o n s t i t u t e s a nearly a t r a u m a t i c w a y of d e t e r m i n i n g o n e i m p o r t a n t c o m p a r t m e n t of C S F flow u n d e r a l m o s t p h y s i o l o g i c c o n d i t i o n s . T h e re producibility w a s g o o d at repeat e x a m i n a t i o n s of t h e s a m e p a t i e n t s i n a clinical s t e a d y state. T h e s l o w i s o t o p e w a s h o u t in patients w i t h d e m e n t i a h a s theoretical interest a n d t h e m e t h o d h a s practical d i a g n o s t i c i m p o r t a n c e in differentiating these patients f r o m , f o r instance, t h o s e w i t h m e n t a l d e p r e s s i o n . It c o n t r i b u t e s t o t h e d i a g n o s i s of disturbances of C S F f l o w and offers possibilities of e s t i m a t i n g the effect of different therapeutic m e a s u r e s o n C S F turnover. 58 - 7 8 5 8 4 1
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T h e t e c h n i q u e f o r r e g i o n a l a n d q u a n t i t a t i v e c i s t e r n o g r a p h y is n o w a d o p t e d t o the u s e of
1 1 1
I n - D T P A a n d a c o m p u t e r assisted g a m m a c a m e r a , w h i c h h a s certain practi
cal a d v a n t a g e s . In a p r e l i m i n a r y series of e x a m i n a t i o n s b y this m e t h o d , straight lines w e r e o b t a i n e d f r o m t h e b a s a l cisterns in s e m i l o g a r i t h m i c p l o t s ( L Y I N G - T U N E L L et coll. 1 9 7 8 ) . T i s s u e b a c k g r o u n d w a s n e g l i g i b l e . C h e l a t e h a s a greater t r a n s e p e n d y m a l diffu s i o n t h a n a l b u m i n w h i c h h a s a m o l e c u l a r w e i g h t a b o u t 1 0 0 t i m e s that of chelate ( H A R B E R T et coll. 1 9 7 3 ) . P A R T A I N et coll. ( 1 9 7 6 ) c o n c l u d e d f r o m their w o r k w i t h m a t h e m a t i c a l m o d e l s t h a t t r a n s m e n i n g e a l t r a n s p o r t w a s t h e m a j o r r o u t e of e l i m i n a m
t i o n of I n - D T P A f r o m C S F , a l t h o u g h t h e r e b y i n v a l i d a t i n g o n e of t h e a s s u m p t i o n s f o r their m o d e l s . T h e fact t h a t the late i m a g e s at i n d i u m c i s t e r n o g r a p h y were s o m e w h a t blurred s u p p o r t s this v i e w . T h e a p p a r e n t diffuse dispersal of
m
I n - D T P A was
c o n s i d e r e d b y SCHOSSBERGER & T O U Y A ( 1 9 7 6 ) a s p r o v i d i n g e v i d e n c e that cisterno g r a p h y d o e s n o t d e m o n s t r a t e C S F f l o w . H o w e v e r , this s t a t e m e n t d o e s n o t s e e m t o b e true for c i s t e r n o g r a p h y u s i n g
1 3 1
I - H S A . First, linear s c a n s d e m o n s t r a t e d a n effective
m o v e m e n t of the activity t o w a r d s t h e c r a n i u m ( L Y I N G - T U N E L L & S O D E R B O R G 1 9 7 2 a). S e c o n d , significant c o r r e l a t i o n s w e r e f o u n d b e t w e e n clearance rate of t h e activity a n d clinical c o n d i t i o n s ; in particular, clearance rates n o r m a l i z e d after
shunting
( F i g . 4 ) . P r o b a b l y c o m p o u n d s of h i g h e r m o l e c u l a r w e i g h t t h a n chelate, s u c h as a l b u m i n or i n u l i n , are m o r e suitable for e v a l u a t i o n of C S F d y n a m i c s , u n d e r the c o n d i t i o n t h a t s u b t r a c t i o n is m a d e for tissue b a c k g r o u n d .
S U M M A R Y
By quantitative cisternography using a stationary detector system with correction for tissue background, an exponential elimination of I - H S A from the basal cisterns was demonstrated, allowing calculation of a biologic half time (BHT) of the clearance curve at a satisfactory level of reproducibility. 'Normal' range of B H T was calculated. Demented patients had significantly longer B H T . In 4 patients with normal pressure hydrocephalus prolonged B H T turned normal after shunting, paralleled by marked clinical improvement, in contrast to previous findings in 4 patients with presenile dementia. The method is now being modified employing ^ I n - D T P A and a computer assisted gamma camera for regional dynamic analysis. 131
Z U S A M M E N F A S S U N G
Durch quantitative Cisternographie unter Anwendung eines stationaren Detector-systems mit Korrektion fur den Gewebehintergrund, wurde eine exponentionelle Elimination von I - H S A von den basalen Cisternen nachgewiesen, die eine Berechnung der biologischen Halbwert Zeit ( B H T ) der Ausscheidungskurve bei einem zufriedenstellenden Niveau von Reproduzierbarkeit erlaubt. Der 'normale' Bereich der B H T wurde berechnet. Demente Patienten hatten eine signifikant langere B H T . Bei 4 Patienten mit Hydrozephalus mit normalem Druck normalisierte sich die verlangerte B H T nach einer Shuntoperation in Parallelitat zu einer bedeutenden klinischen Verbesserung im Gegensatz zu friiheren Befunden bei 4 Patienten mit praseniler D e m e n s . D i e Methode ist nun verandert unter A n wendung v o n I n - D T P A und einer Computer-unterstiitzten Gammakamera fiir eine regionale dynamische Analyse. 1 3 1
l n
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R E S U M E
La cisternographie quantitative utilisant un systeme de detecteur stationnaire avec correc tion pour le bruit de fond des tissus, a permis de mettre en evidence une elimination exponentielle de I - H S A a partir des citernes basales, permettant de calculer une demi-vie biologique (BHT) de la courbe de clearance avec un niveau satisfaisant de reproductibilite. Les auteurs ont calcule un intervalle 'normal' de B H T . Les patients dements ont une B H T significativement plus longue. Chez 4 malades atteints d'hydrocephalie a pression normale, la B H T prolongee est revenue a la normale apres derivation, accompagnee par une ameliora tion clinique importante et contrastant avec les resultats obtenus precedemment chez 4 malades atteints de demencj pre-senile. Cette methode est maintenant modifiee en utilisant I n - D T P A et une gamma-camera assistee par ordinateur pour une analyse dynamique regionale. 131
l u
R E F E R E N C E S
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R I S A t o circulating plasma.
AKERMAN M., DE TOVAR G . and G U I O T G . : Radioisotope cisternography and ventriculo
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