Magnetite in the body
5
Proc. Natl. Acad. Sci. USA Vol. 8 9 , p p . 7683-7687, August 1992 Biophysics Magnetite biomineralization i n t h e human brain (iron/extremely l ow frequencymagnetic fields) JOSEPH L . KIRSCHVINK, ATSUKO KOBAYASHI-KIRSCHVINK, A N D BARBARA J . WOODFORD* Division ofGeological a n d Planetary Sciences, T he California Institute o f Technology, Pasadena, CA 91125 Communicated b y Leon T . Silver, Ma y 7 , 1992 ABSTRACT Although t h e mineral magnetite (Fe3O4) i s precipitated biochemically b y bacteria, protists, a n d a variety o f animals, i t h a s n o t been documented previously i n human tissue. Using a n ultrasensitive superconducting magnetometer i n a clean-lab environment, w e have detected the presence o f ferromagnetic material i n a variety o f tissues from t h e human brain. Magnetic particle extracts from solubilized brain tissues examined with high-resolution transmission electron micros- copy, electron diffraction, a n d elemental analyses identify minerals i n t h e magnetitemaghemite family, with many o f t h e crystal morphologies an d structures resembling strongly those precipitated b y magnetotactic bacteria a n d fish. These mag- netic a n d high-resolution transmission electron microscopy measurements imply th e presence of a minimum o f 5 million single-domain crystals p e r gram f o r most tissues i n t he brain a n d >100 million crystals p e r gram f o r p ia a n d dura. Magnetic property data indicate th e crystals a r e i n clumps of between 50 a n d 1 0 0 particles. Biogenic magnetite i n t h e human brain m a y account f o r high-field saturation effects observed i n t he T i a n d T 2 values o f magnetic resonance imaging and, perhaps, f o r a variety o f biological effects o f low-frequency magnetic fields. I n past studies o f iron storage a n d magnetic resonance imaging (MRI), i t h a s been assumed universally that there a r e n o permanently magnetized (ferromagnetic) materials pre- sent i n human tissues ( 1 , 2 ). Similar assumptions have been made i n virtually all biophysical assessments of human risk associated with exposure t o static a n d extremely low- frequency magnetic fields ( 3 ) a n d b y critics ( 4 ) of epidemio- logical studies that suggest links between weak power-line- frequency magnetic fields a n d various human disorders ( 5 , 6 ). These analyses have focused on the side effects o f electrical induction or possible diamagnetic a n d paramagnetic interac- tions. However, theferrimagnetic mineral magnetite (Fe3O4) i s formed biochemically b y many living organisms. Because ferromagnetic crystals interact more than a million times more strongly with external magnetic fields than do diamag- netic o r paramagnetic materials o f similar volume, earth- strength magnetic fields c a n yield many responses that stand above thermal noise (7). Hence, t he assumption implicit i n past studies that human tissues a r e free o f ferromagnetic material needs t o b e reassessed critically a n d tested experi- mentally. Previous searches f o r biogenic magnetite i n human tissues have n o t been conclusive ( 8 , 9 ) . Despite this, extensive research over the past 3 0 years h a s demonstrated that many organisms have t he biochemical ability to precipitate t he ferrimagnetic minerals magnetite (Fe3O4) (10-16) a n d greigite (Fe3S4) (17). I n terms of i ts phyletic distribution, magnetite biomineralization is particularly widespread, having been documented i n monerans (10), protists (11), a n d animals (12-16), with a fossil record extending back into Precambrian time (18). Within Kingdom Animalia, i t is known within t he mollusks (12), arthropods (13), a n d chordates (14, 1 5 ) an d is suspected i n many more groups (16). I n t h e microorganisms (10, 1 1 ) a n d fish (15), linear chains o f membrane-bound crystals o f magnetite (magnetosomes) form structures best described as "biological bar magnets." We report here that human tissues possess similar crystals of biogenic magnetite, with minimum estimates between 5 a n d 100 million single-domain crystals p e r gram i n th e tissues of t h e human brain. Magnetic particle extracts from solubi- lized tissues examined with high-resolution transmission electron microscopy (TEM) a n d electron diffraction identify minerals i n th e magnetite-maghemite solid solution, with many crystal morphologies a n d structures resembling those precipitated b y magnetotactic bacteria a n d fish. MATERIALS AND METHODS Tissue Samples. Human brain material w a s obtained 12-24 h postmortemfrom t h e Alzheimer'sDiseaseResearch Center Consortium o f Southern California. Samples o f brain a n d meninges were dissected using acid-cleaned ceramic or Tef- lon-coated instruments. These tissues were placed into 7 0 % ethanol [made with deionized water a n d filtered through a (pore-size) Millipore filter] i n containers that h a d previously been cleaned with 2 M HCl. Samples from seven brains were obtained from patients whose ages averaged 65 years a n d ranged from 4 8 t o 8 8 years. Four o f these were from suspected Alzheimer disease patients. Cerebral cortical areas a n d cerebellum were included f o r a l l seven brains. n o n e case, brain a n d spinal dura, basal ganglia, an d midbrain and, i n another case, olfactory bulbs, superior sagittal sinus, a n d tentorium of t h e dura were obtained i n addition t o t h e above tissues. Magnetometry. Subsamples fo r magnetic measurements were removed from t h e tissues b y using similar tools i n a magnetically shielded dust-free clean laboratory (19). Mea- surements of ferromagnetic materials were made using a magnetometer employing Rf-biased superconducting quan- t u m interference devices (SQUIDs), designed t o measure t h e total ferromagnetic moment o f samples placed within a Helmholtz-coil pickup loop (20). Samples were fastened t o a thin acid-washed monofilament string, a n d a stepping motor moved the sample vertically between t h e magnetization a n d demagnetization coils a n d t h e measurement region o f t h e SQUID magnetometer. Several magnetic analyses borrowed from th e field o f rock a n d mineral magnetism (21-23) were performed routinely on frozen tissue samples t o determine t h e concentration, mineralogy, a n d packing geometry o f a n y ferromagnetic materials present. Abbreviations: MRI, magnetic resonance imaging; SQUID, super- conducting quantum interference device; TEM, transmission elec- tron microscopy; IRM, isothermal remanent magnetization; ARM, anhysteretic remanent magnetization. *Present address: Department o f Anatomy a n d Cell Biology, Uni- versity o f Southern California, 1333 S a n Pablo Street, L o s Angeles, C A 90033. 7683 T h e publication costs o f this article were defrayed i n part b y page charge payment. This article must therefore b e hereby marked "advertisement" i n accordance with 1 8 U.S.C. §1734 t o indicate this fact.
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Transcript of Magnetite in the body
8/8/2019 Magnetite in the body
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P r o c . N a t l . A c a d . S c i . USAV o l . 8 9 , p p . 7 6 8 3 - 7 6 8 7 , A u g u s t 1 9 9 2B i o p h y s i c s
M a g n e t i t e b i o m i n e r a l i z a t i o n i n t h e human b r a i n( i r o n / e x t r e m e l y l o w f r e q u e n c y m a g n e t i c f i e l d s )
J O S E P H L . K I R S C H V I N K , ATSUKO K O B A Y A S H I - K I R S C H V I N K , AND BARBARA J . WOODFORD*
D i v i s i o n o f G e o l o g i c a l a n d P l a n e t a r y S c i e n c e s , T h e C a l i f o r n i a I n s t i t u t e o f T e c h n o l o g y , P a s a d e n a , CA 9 1 1 2 5
C o m m u n i c a t e d b y L e o n T . S i l v e r , May 7 , 1 9 9 2
ABSTRACT A l t h o u g h t h e m i n e r a l m a g ne t i te ( F e3 O4 ) i sp r e c i p i t a t e d b i o c h e m i c a l l y b y b a c t e r i a , p r o t i s t s , a n d a v a r i e t yo f a n i m a l s , i t h a s n o t b e e n d o c u m e n t e d p r e v i o u s l y i n human
t i s s u e . U s i n g a n u l t r a s e n s i t i v e s u p e r c o n d u c t i n g m a g n e t o m e t e r
i n a c l e a n - l a b e n v i r o n m e n t , we h a v e d et e c t e d t h e p r e s e n c e o f
f e r r o m a g n e t i c m a t e r i a l i n a v a r i e t y o f t i s s u e s f r o m t h e humanb r a i n . M a g n e t i c p a r t i c l e e x t r a c t s f r o m s o l u b i l i z e d b r a i n t i s s u e se x a m i n e d w i t h h i g h - r e s o l u t i o n t r a n s m i s s i o n e l e c t r o n m i c r o s -
c o p y , e l e c t r o n d i f f r a c t i o n , a n d e l e m e n t a l a n a l y s e s i d e n t i f ym i n e r a l s i n t h e m a g n e t i t e m a g h e m i t e f a m i l y , w i t h many o f t h ec r y s t a l m o r p h o l o g i e s a n d s t r u c t u r e s r e s e m b l i n g s t r o n g l y t h o s ep r e c i p i t a t e d b y m a g n e t o t a c t i c b a c t e r i a a n d f i s h . T h e s e m a g -
n e t i c a n d h i g h - r e s o l u t i o n t r a n s m i s s i o n e l e c t r o n m i c r o s c o p ym e a s u r e m e n t s i m p l y t h e p r e s e n c e o f a minimum o f 5 m i l l i o ns i n g l e - d o m a i n c r y s t a l s p e r g r a m f o r m o s t t i s s u e s i n t h e b r a i n
a n d > 1 0 0 m i l l i o n c r y s t a l s p e r g r a m f o r p i a a n d d u r a . M a g n e t i cp r o p er t y d a t a i n d i c a t e t h e c r y s t a l s a r e i n c l u m p s o f b e t w e en 5 0
a n d 1 0 0 p a r t i c l e s . B i o g e n i c m a g n e t i t e i n t h e human b r a i n maya c c o u n t f o r h i g h - f i e l d s a t u r a t i o n e f f e c t s o b s e r v e d i n t h e T i a n dT 2 v a l u e s o f m a g n e t i c r e s o n a n c e i m a g i n g a nd , p e r h ap s , f o r a
v a r i e t y o f b i o l o g i c a l e f f e c t s o f l o w - f r e q u e n c y m a g n e t i c f i e l d s .
I n p a s t s t u d i e s o f i r o n s t o r a g e a n d m a g n e t i c r e s o n a n c e
i m a g i n g ( M R I ) , i t h a s b e e n a s s u m e d u n i v e r s a l l y t h a t t h e r e a r e
n o p e r m a ne n t l y m a g n e t iz e d ( f e r r o m a g n e t i c ) m a t e r i a l s p r e -s e n t i n human t i s s u e s ( 1 , 2 ) . S i m i l a r a s s u m p t i o n s h a v e b e e nm a d e i n v i r t u a l l y a l l b i o p h y s i c a l a s s e s s m e n t s o f human r i s k
a s s o c i a t e d w i t h e x p o s u r e t o s t a t i c a n d e x t r e m e l y l o w -f r e q u e n c y m a g n e t i c f i e l d s ( 3 ) a n d b y c r i t i c s ( 4 ) o f e p i de m i o -l o g i c a l s t u d i e s t h a t s u g g e s t l i n k s b e t w e e n w e a k p o w e r - l i n e -f r e q u e n c y m a g n e t i c f i e l d s a n d v a r i o u s h u m a n d i s o r d e r s ( 5 , 6 ) .T h e s e a n a l y s e s h a v e f o c u s e d o n t h e s i d e e f f e c t s o f e l e c t r i c a li n d u c t i o n o r p o s s i b l e d i a m a g n e t i c a n d p a r a m a g n e t i c i n t e r a c -t i o n s . H o w e v e r , t h e f e r r i m a g n e t i c m i n e r a l m a g n e t i t e ( F e 3 O 4 )i s f o r m e d b i o c h e m i c a l l y b y many l i v i n g o r g a n i s m s . B e c a u s ef e r r o m a g n e t i c c r y s t a l s i n t e r a c t m o r e t h a n a m i l l i o n t i m e s
m o r e s t r o n g l y w i t h e x t e r n a l m a g n e t i c f i e l d s t h a n d o d i a m a g -n e t i c o r p a r a m a g n e t i c m a t e r i a l s o f s i m i l a r v o l u m e , e a r t h -s t r e n g t h m a g n e t i c f i e l d s c a n y i e l d many r e s p o n s e s t h a t s t a n da b o v e t h e r m a l n o i s e ( 7 ) . H e n c e , t h e a s s u m p t i o n i m p l i c i t i np a s t s t u d i e s t h a t human t i s s u e s a r e f r e e o f f e r r o m a g n e t i cm a t e r i a l n e e d s t o b e r e a s s e s s e d c r i t i c a l l y a n d t e s t e d e x p e r i -m e n t a l l y .
P r e v i o u s s e a r c h e s f o r b i o g e n i c m a g n e t i t e i n h u m a n t i s s u e sh a v e n o t b e e n c o n c l u s i v e ( 8 , 9 ) . D e s p i t e t h i s , e x t e n s i v er e s ea r c h o v e r t h e p a s t 3 0 y e a r s h a s d e m o n s t r a t e d t h a t manyo r g a n i s m s h a v e t h e b i o c h e m i c a l a b i l i t y t o p r e c i p i t a t e t h ef e r r i m a g n e t i c m i n e r a l s m a g n e t i t e ( F e 3 O 4 ) ( 1 0 - 1 6 ) a n d g r e i g i t e( F e 3 S 4 ) ( 1 7 ) . I n t e r m s o f i t s p h y l e t i c d i s t r i b u t i o n , m a g n e t i t eb i o m i n e r a l i z a t i o n i s p a r t i c u l a r l y w i d e s p r e a d , h a v i n g b e e nd o c u m e n t e d i n m o n e r a n s ( 1 0 ) , p r o t i s t s ( 1 1 ) , a n d a n i m a l s
( 1 2 - 1 6 ) , w i t h a f o s s i l r e c o r d e x t e n d i n g b a c k i n t o P r e c a m b r i a nt i m e ( 1 8 ) . W i t h i n K i n g d o m A n i m a l i a , i t i s known w i t h i n t h e
m o l l u s k s ( 1 2 ) , a r t h r o p o d s ( 1 3 ) , a n d c h o r d a t e s ( 1 4 , 1 5 ) a n d i ss u s p e c t e d i n m a n y m o r e g r o u p s ( 1 6 ) . I n t h e m i c r o o r g a n i s m s
( 1 0 , 1 1 ) a n d f i s h ( 1 5 ) , l i n e a r c h a i n s o f m e m b r a n e - b o u n dc r y s t a l s o f m a g n e t i t e ( m a g n e t o s o m e s ) f o r m s t r u c t u r e s b e s t
d e s c r i b e d a s " b i o l o g i c a l b a r m a g n e t s . "We r e p o r t h e r e t h a t h u m a n t i s s u e s p o s s e s s s i m i l a r c r y s t a l s
o f b i o g e n i c m a g n e t i t e , w i t h minimum e s t i m a t e s b e t w e e n 5a n d 1 0 0 m i l l i o n s i n g l e - d o m a i n c r y s t a l s p e r g r a m i n t h e t i s s u e so f t h e human b r a i n . M a g n e t i c p a r t i c l e e x t r a c t s f r o m s o l u b i -l i z e d t i s s u e s e x a m i n e d w i t h h i g h - r e s o l u t i o n t r a n s m i s s i o ne l e c t r o n m i c r o s c o p y ( T E M ) a n d e l e c t r o n d i f f r a c t i o n i d e n t i f ym i n e r a l s i n t h e m a g n e t i t e - m a g h e m i t e s o l i d s o l u t i o n , w i t h
m a n y c r y s t a l m o r p h o l o g i e s a n d s t r u c t u r e s r e s e m b l i n g t h o s ep r e c i p i t a t e d b y m a g n e t o t a c t i c b a c t e r i a a n d f i s h .
MATERIALS AND METHODS
T i s s u e S a m p l e s . Human b r a i n m a t e r i a l w a s o b t a i n e d 1 2 - 2 4h p o s t m o r t e m f r o m t h e A l z h ei m er ' s D i s e as e R e s e a r c h C e n t e rC o n s o r t i u m o f S o u t h e r n C a l i f o r n i a . S a m p l e s o f b r a i n a n dm e n i n g e s w e r e d i s s e c t e d u s i n g a c i d - c l e a n e d c e r a m i c o r T e f -l o n - c o a t e d i n s t r u m e n t s . T h e s e t i s s u e s w e r e p l a c e d i n t o 70%e t h a n o l [ m a d e w i t h d e i o n i z e d w a t e r a n d f i l t e r e d t h r o u g h a
2 0 0 - n m ( p o r e - s i z e ) M i l l i p o r e f i l t e r ] i n c o n t a i n e r s t h a t h a dp r e v i o u s l y b e e n c l e a n e d w i t h 2 M H C l . S a m p l e s f r o m s e v e n
b r a i n s w e r e o b t a i n e d f r o m p a t i e n t s w h o s e a g e s a v e r a g e d 6 5
y e a r s a n d r a n g e d f r o m 4 8 t o 8 8 y e a r s . F o u r o f t h e s e w e r e f r o m
s u s p e c t e d A l z h e i m e r d i s e a s e p a t i e n t s . C e r e b r a l c o r t i c a l a r e a sa n d c e r e b e l l u m w e r e i n c l u d e d f o r a l l s e v e n b r a i n s . I n o n e
c a s e , b r a i n a n d s p i n a l d u r a , b a s a l g a n g l i a , a n d m i d b r a i n a n d ,i n a n o t h e r c a s e , o l f a c t o r y b u l b s , s u p e r i o r s a g i t t a l s i n u s , a n dt e n t o r iu m o f t h e d u r a w e r e o b t a i n e d i n a d d i t i o n t o t h e a b o v et i s s u e s .
M a g n e t o m e t r y . S u b s a m p l e s f o r m a g n e t i c m e a s u r e m e n t s
w e r e r e m o v e d f r o m t h e t i s s u e s b y u s i n g s i m i l a r t o o l s i n a
m a g n e t i c a l l y s h i e l d e d d u s t - f r e e c l e a n l a b o r a t o r y ( 1 9 ) . M e a -s u r e m e n ts o f f e r r o m a g n e t i c m a t e r i a l s w e r e m a d e u s i n g a
m a g n e t o m e t e r e m p l o y i n g R f - b i a s e d s u p e r c o n d u c t i n g q u a n -t u m i n t e r f e r e n c e d e v i c e s ( S Q U I D s ) , d e s i g n e d t o m e a s u r e t h et o t a l f e r r o m a g n e t i c moment o f s a m p l e s p l a c e d w i t h i n a
H e l m h o l t z - c o i l p i c k u p l o o p ( 2 0 ) . S a m p l e s w e r e f a s t e n e d t o a
t h i n a c i d - w a s h e d m o n o f i l a m e n t s t r i n g , a n d a s t e p p i n g m o t o r
m o v e d t h e s a m p l e v e r t i c a l l y b e t w e e n t h e m a g n e t i z a t i o n a n dd e m a g n e t i z a t i o n c o i l s a n d t h e m e a s u r e m e n t r e g i o n o f t h eSQUID m a g n e t o m e t e r . S e v e r a l m a g n e t i c a n a l y s e s b o r r o w e df r o m t h e f i e l d o f r o c k a n d m i n e r a l m a g n e t i s m ( 2 1 - 2 3 ) w e r e
p e r f o r m e d r o u t i n e l y o n f r o z e n t i s s u e s a m p l e s t o d e t e r m i n e
t h e c o n c e n t r a t i o n , m i n e r a l o g y , a n d p a c k i n g g e o m e t r y o f a n yf e r r o m a g n e t i c m a t e r i a l s p r e s e n t .
A b b r e v i a t i o n s : M R I , m a g n e t i c r e s o n a n c e i m a g i n g ; S Q U I D , s u p e r -c o n d u c t i n g q u a n t u m i n t e r f e r e n c e d e v i c e ; TEM, t r a n s m i s s i o n e l e c -t r o n m i c r o s c o p y ; I R M , i s o t h e r m a l r e m a n e n t m a g n e t i z a t i o n ; ARM,a n h y s t e r e t i c r e m a n e n t m a g n e t i z a t i o n .* P r e s e n t a d d r e s s : D e p a r t m e n t o f A n a t o m y a n d C e l l B i o l o g y , U n i -
v e r s i t y o f S o u t h e r n C a l i f o r n i a , 1 3 3 3 S a n P a b l o S t r e e t , L o s A n g e l e s ,CA 9 0 0 3 3 .
7 6 8 3
T h e p u b l i c a t i o n c o s t s o f t h i s a r t i c l e w e r e d e f r a y e d i n p a r t b y p a g e c h a r g e
p a y m e n t . T h i s a r t i c l e m u s t t h e r e f o r e b e h e r e b y m a r k e d " a d v e r t i s e m e n t "
i n a c c o r d a n c e w i t h 1 8 U . S . C . § 1 7 3 4 s o l e l y t o i n d i c a t e t h i s f a c t .
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7 6 8 4 B i o p h y s i c s : K i r s c h v i n k e t a l .
S a m p l e P r e p a r a t i o n f o r t h e M a g n e t o m e t e r . P i a a n d b l o o dv e s s e l s w e r e r e m o v e d f r o m a l l s a m p l e s o f t h e m e n i n g e s
b e f o r e a n a l y s i s i n t h e SQUID m a g n e t o m e t e r . Two p r e p a r a -t i o n m e t h o d s w e r e u s e d . L a r g e i n t a c t s a m p l e s o f t h e c e r e b r a lc o r t e x a n d c e r e b e l l u m w e r e f r o z e n d i r e c t l y i n l i q u i d n i t r o g e n .B r a i n t i s s u e s t h a t f r a c t u r e d u p o n f r e e z i n g o r d i s s e c t i o n w e r e
p l a c e d i n t o a p r e v i o u s l y a c i d - c l e a n e d i c e - c u b e m o l d a n df r o z e n i n t o b l o c k s w i t h s m a l l q u a n t i t i e s o f n o n m a g n e t i c
d e i o n i z e d w a t e r . E i t h e r t h e f r o z e n p i e c e o f b r a i n o r t h e
i c e / b r a i n b l o c k w a s a t t a c h e d b y a s l i p k n o t t o t h e m o n o f i l -a m e n t l i n e a n d t h e n c e n te r e d w i t h i n t h e c o l u m n o f t h e SQUIDm a g n e t o m e t e r . B a c k g r o u n d i n s t r u m e n t n o i s e a n d t h e l e v e l so f l a b o r a t o r y c o n t a m i n a n t s w e r e m o n i t o r e d w i t h b l a n k 1 5 - gi c e c u b e s o f d i s t i l l e d d e i o n i z e d w a t e r ; t y p i c a l i c e - c u b e b a c k -
g r o u n d n o i s e l e v e l s w e r e i n t h e r a n g e o f 2 x 1 0 - 8 A m 2 k g - 1 .A l l a q u e o u s s o l u t i o n s u s e d i n s a m p l e h a n d l i n g w e r e p a s s e d
t h r o u g h 2 0 0 - n m f i l t e r s . A l l s o l u t i o n s , i n c l u d i n g t h e t o l u e n ea n d t i s s u e s o l u b i l i z e r s , w e r e c l e a n e d m a g n e t i c a l l y b y s t o r i n gf o r a t l e a s t 2 w e e k s p r i o r t o u s e i n c o n t a i n e r s w i t h l a r g eh i g h - i n t e n s i t y NdFeB m a g n e t s s t r a p p e d t o t h e i r b a s e t o a i d i nt h e r e m o v a l o f a n y p r e e x i s t i n g f e r r o m a g n e t i c c o n t a m i n a n t s .
E x t r a c t i o n a n d E l e c t r o n M i c r o s c o p y . E x t r a c t i o n d e v i c e sm a d e f r o m P y r e x w e ig h in g v i a l s w e r e u s e d t o r e m o v e t h em a g n e t i c p a r t i c l e s f r o m t h e b r a i n t i s s u e s . T h e g r o u n d - g l a s s
c a p s w e r e m o d i f i e d b y g l a s s b l o w i n g t o m a k e a t h i n - w a l l e dc y l i n d r i c a l f i n g e r , s e a l e d o n t h e b o t t o m , e x t e n d i n g f r o m t h ec a p a b o ut 2 / 3 o f t h e d i s t a n c e i n t o t h e v i a l . T i s s u e s w e r ed i g e s t e d i n m a g n e t i c a l l y c l e a n e d c o m m e r c i a l s o l u t i o n s o ft o l u e n e / q u a t e r n a r y ammonium h y d r o x i d e ( e . g . , B e c k m a nt i s s u e s o l u b i l i z e r ) , 4:5 ( v o l / v o l ) f o r a m i n i m u m p e r i o d o f 1w e e k w h i l e e x p o s e d t o t h e s t r o n g f i e l d o f a NdFeB m a g n e ti n s e r t e d w i t h i n t h e f i n g e r . T h e v i a l c a p a n d m a g n e t i c f i n g e rw e r e t h e n r i n s e d i n c l e a n t o l u e n e , t h e m a g n e t i c a g g r e g a t e sw e r e r e d i s p e r s e d m e c h a n i c a l l y i n 0 . 2 5 m l o f t o l u e n e , a n ds m a l l d r o p s w e r e p l a c e d o n c a r b o n - c o a t e d c o p p e r g r i d s f o rh i g h - r e s o l u t i o n TEM a n a l y s i s . S a m p l e s w e r e e x a m i n e d a th i g h r e s o l u t i o n o n a P h i l l i p s m o d e l 4 3 0 3 0 0 - k V h i g h -r e s o l u t i o n TEM w i t h a n e n e r g y - d i s p e r s i v e x - r a y a n a l y s i ss y s t e m f o r e l e m e n t a l d e t e r m i n a t i o n s . M i n e r a l o g i c a s s i g n -
T a b l e 1 . Mean s a t u r a t e d IR M f o r c e r e b r a l c o r t e x a n d c e r e b e l l u m
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1 0 . 1 4 ± 0 . 0 8 3 . 0 ± 1 . 4 1 12 0 . 1 8 ± 0 . 1 0 3 . 9 ± 2 . 2 53 0 . 1 4 ± 0 . 0 5 3 . 0 ± 1 . 1 54 0 . 2 7 0 . 2 1 5 . 9 4 . 6 6
5 0 . 2 0 0 . 0 9 4 . 3 2 . 0 36 0 . 1 9 4 . 1 17 0 . 3 3 0 . 1 9 7 . 2 ± 4 . 1 2
M e n i n g e s1 2 . 5 ± 1 . 8 5 4 ± 3 9 8
2 2 . 5 1 . 5 5 4 3 3 86 5 . 0 1 0 9 1
D a t a f o r s a t u r a t e d IRM a r e e x p r e s s e d a s g A m 2 k g - 1 ( w e t w e i g h t )( m e a n ± S D ) . O c c i p i t a l s a m p l e s w e r e f r o m B r o d m a n a r e a s ( B . A . ) 1 7 ,1 8 , a n d 1 9 ; t e m p o r a l s a m p l e s w e r e f r o m B . A . 2 0 , 2 1 , a n d 2 2 ; p a r i e t a ls a m p l e s w e r e f r o m B . A . 3 , 1 , 2 , 5 , a n d 7 ; a n d f r o n t a l s a m p l e s w e r ef r o m B . A . 4 a n d 6 . S a m p l e s i z e s r a n g e d f r o m 0 . 5 g t o 2 2 g . T h em e n i n g e s f r o m s a m p l e s o f b r a i n s 1 , 2 , a n d 6 w e r e a n a l y z e d s e p a -r a t e l y . T h e i c e - c u b e t e c h n i q u e w a s u s e d f o r a l l o f t h e m e n i n g e s , a n do n t h e t i s s u e s f r o m b r a i n 2 , a n d f o r 7 o f t h e 1 1 s a m p l e s f r o m b r a i n 1 ;n o d i f f e r e n c e i n r e s u l t s w a s s e e n w i t h t h i s t e c h n i q u e . M a g n e t i t ec o n c e n t r a t i o n s w e r e e s t i m a t e d b y n o t i n g t h a t t h e s a t u r a t i o n r e m a -n e n c e s h o u l d b e e x a c t l y h a l f o f t h e s a t u r a t i o n m a g n e t i z a t i o n f o r a
d i s p e r s i o n o f s i n g l e - d o m a i n c r y s t a l s ( 2 1 ) . B r a i n s 1 - 4 w e r e f r o mn o r m a l p a t i e n t s , b r a i n s 5 a n d 6 w e r e c o n f i r m e d A l z h e i m e r p a t i e n t s ,a n d b r a i n 7 w a s a s u s p e c t e d A l z h e i m e r p a t i e n t .
m e n t s w e r e m a d e b y i n d e x i n g t h e s p o t p a t t e r n s p r o d u c e d b ys e l e c t e d - a r e a e l e c t r o n d i f f r a c t i o n o n i n d i v i d u a l m i n e r a l g r a i n sa n d o n r i n g s f r o m p o w d e r p a t t e r n s , w i t h c a l i b r a t i o n a g a i n s ta g o l d f i l m s t a n d a r d . An e s t i m a t e o f t h e g r a i n - s i z e d i s t r i b u t i o nw a s m a d e b y m e a s u r i n g t h e l e n g t h a n d w i d t h o f 7 0 c r y s t a ls h a d o w s f r o m a l a r g e c l u m p . C o n t r o l s a m p l e s c o n s i s t i n g o f
t h e s o l u t i o n s w i t h o u t b r a i n t i s s u e s , a s w e l l a s t h e s o l u t i o n ss p i k e d w i t h k n o w n q u a n t i t i e s o f b a c t e r i a l m a g n e t i t e , w e r e r u n
t o c h e c k f o r c o n t a m i n a n t s i n t h e s o l v e n t s a s w e l l a s t od e t e r m i n e
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o f b a c t e r i a l m a g n e t i t e s .
RESULTS
M a g n e t o m e t r y . A l l o f t h e t i s s u e s e x a m i n e d h a d i s o t h e r m a lr e m a n e n t m a g n e t i z a t i o n s ( I R M s ) t h a t s a t u r a t e d i n a p p l i e df i e l d s o f - 3 0 0 m T , a c h a r a c t e r i s t i c p r o p e r t y o f t h e m a g n e t i t e -m a g h e m i t e s e r i e s . T h e a b i l i t y t o g a i n a n d l o s e r e m a n e n tm a g n e t i z a t i o n i n t h e s e e x p e r i m e n t s i s a d e f i n i t i v e c h a r a c t e r -i s t i c o f f e r r o m a g n e t i c m a t e r i a l s . T a b l e 1 s h o w s t h e m e a nv a l u e s f o r e a c h b r a i n . T h e a v e r a g e m a g n e t i z a t i o n i n d i c a t e st h e e q u i v a l e n t o f =4 n g o f m a g n e t i t e p e r g r a m o f t i s s u e . I nc o n t r a s t , a v e r a g e v a l u e s f o r t h e m e n i n g e s f r o m t h r e e b r a i n s( T a b l e 1 ) a r e n e a r l y 2 0 t i m e s h i g h e r , o r - 7 0 n g / g . F o rc o m p a r i s o n , m e a s u r e m e n t s o f IRM f r o m t r i p l e - d i s t i l l e dd e i o n i z e d i c e c u b e s y i e l d a b a c k g r o u n d " n o i s e " o f = 0 . 5n g / g .
T h e r e w a s r e m a r k a b l e c o n s i s t e n c y i n t h e IRM m e a s u r e -
m e n t s f o r b o t h t h e b r a i n t i s s u e a n d t h e m e n i n g e s . T h e r e w a sl i t t l e d i f f e r e n c e i n IRM f r o m o n e a r e a o f c e r e b r a l c o r t e x t oa n o t h e r o r i n t h e c e r e b r a l v e r s u s t h e c e r e b e l l a r c o r t e x .D i f f e r e n c e s b e t w e e n t i s s u e s f r o m t h e n o r m a l b r a i n s v e r s u s
t h o s e s u s p e c t e d o r c o n f i r m e d t o b e A l z h e i m e r d i s e a s e c a s e s
w e r e n e g l i g i b l e . A r e a s o f t h e b r a i n p r e v i o u s l y r e p o r t e d t oh a v e h i g h i r o n c o n t e n t i n c l u d e t h e d e n t a t e n u c l e u s , t h e b a s a lg a n g l i a , a n d a r e a s o f t h e m i d b r a i n ( 2 4 ) . S a m p l e s o f t h e s ea r e a s h a d n o g r e a t e r c o n t e n t o f m a g n e t i c p a r t i c l e s t h a n d i dt h e c e r e b e l l a r o r c e r e b r a l c o r t e x .
F i g . 1 s h o w s m a g n e t i c p r o p e r t i e s f o r r e p r e s e n t a t i v e t i s -s u e s , i n c l u d i n g c o e r c i v i t y d e t e r m i n a t i o n s ( 2 0 ) ( F i g . 1 A ) a n d
a t e s t f o r i n t e r g r a i n i n t e r a c t i o n e f f e c t s u s i n g t h e a n h y s t e r e t i cr e m a n e n t m a g n e t i z a t i o n ( 2 3 ) (ARM, F i g . 1 B ) . M e d i a n c o e r -c i v i t y v a l u e s w e r e -3 0 m T , b u t r a n g e d f r o m 1 2 ( p i a f r o mc e r e b e l l u m ) t o 5 0 ( b a s a l g a n g l i a ) m T , w e l l w i t h i n t h e c o e r -c i v i t y r a n g e f o r s i n g l e - d o m a i n m a g n e t i t e . T h e s h i f t i n c o e r -c i v i t y d i s t r i b u t i o n s , a s m e a s u r e d b y IRM a c q u i s i t i o n a n d i t sd e m a g n e t i z a t i o n , a n d t h e r e l a t i v e l y s l o w t e n d e n c y t o a c q u i r ea n ARM s u g g e s t t h a t t h e p a r t i c l e s i n s i t u a r e i n s m a l li n t e r a c t i n g c l u m p s . C o m p a r i s o n w i t h b a c t e r i a l c o n t r o l s a m -
p l e s s u g g e s t s b e t w e e n 5 0 a n d 1 0 0 p a r t i c l e s p e r c l u m p .Extton a n d E l e c t r o n M i c r o s c o p y . When v i e w e d u n d e r
l o w p o w e r t h r o u g h a n o p t i c a l d i s s e c t i n g m i c r o s c o p e , b l a c k
s t r i n g s o f a g g r e g a t e d p a r t i c l e s e x t r a c t e d f r o m b r a i n t i s s u e sa r e s e e n c o l l e c t e d a t t h e f o c u s o f t h e m a g n e t i c f i n g e r d e v i c e .I n s h a p e a n d m o r p h o l o g y , t h e s e a g g r e g a t i o n s a r e i n d i s t i n -
g u i s h a b l e f r o m s i m i l a r a g g r e g a t e s f r o m t h e m a g n e t o t a c t i cb a c t e r i a l c o n t r o l s . No m a g n e t i c a g g r e g a t e s w e r e o b s e r v e d t oc o l l e c t i n t h e b l a n k t i s s u e - f r e e c o n t r o l s a m p l e s . R o u g h v o l -ume e s t i m a t e s o f t h e e x t r a c t e d m a t e r i a l , m a d e b y m e a s u r i n gt h e l e n g t h a n d w i d t h o f t h e a g g r e g a t e s a n d t o t a l i n g f o r e a c hc h a i n , a g r e e t o w i t h i n a n o r d e r o f m a g n i t u d e w i t h e s t i m a t e sf r o m t h e IRM m e a s u r e m e n t s , i m p l y i n g t h a t t h e e x t r a c t i o nt e c h n i q u e w a s r e a s o n a b l y e f f i c i e n t .
F i g . 2 s h o w s t w o r e p r e s e n t a t i v e c r y s t a l m o r p h o l o g i e s o ft h e e x t r a c t e d m a g n e t i c p a r t i c l e s . G r a i n s i z e s w e r e b i m o d a l ,w i t h 6 2 o f t h e 7 0 m e a s u r e d c r y s t a l s i n t h e 1 0 - t o 7 0 - n m r a n g ea n d t h e r e m a i n i n g 8 w i t h s i z e s r a n g i n g f r o m 9 0 t o 2 0 0 n m .M e a s u r e m e n t s o f t h e TEM s h a d o w s f r o m 6 2 o f t h e s m a l l e rp a r t i c l e s i n o n e a g g r e g a t e y i e l d e d a n a v e r a g e s i z e o f 3 3 . 4 +
1 5 . 2 n m . N o t e t h a t t h i s mean v a l u e m u s t b e b i a s e d t o w a r d
P r o c . N a t l . A c a d . S c i . USA 8 9 ( 1 9 9 2 )
8/8/2019 Magnetite in the body
http://slidepdf.com/reader/full/magnetite-in-the-body 3/5
P r o c . N a t l . A c a d . S c i . USA 8 9 ( 1 9 9 2 ) 7 6 8 5
l a r g e r s i z e s b e c a u s e t h e e x t r a c t i o n p r o c e d u r e w i l l d i s c r i m i -n a t e a g a i n s t v e r y s m a l l p a r t i c l e s t h a t move m o r e s l o w l y
t h r o u g h t h e l i q u i d . S i z e a n d s h a p e r e l a t i o n s h i p s f o r a l lm e a s u r e d p a r t i c l e s f a l l w i t h i n t h e s i n g l e - d o m a i n a n d s u p e r -
p a r a m a g n e t i c f i e l d s f o r m a g n e t i t e ( 2 5 ) . C r y s t a l v o l u m e e s t i -m a t e s , d o n e b y a s s u m i n g e q u a n t p a r t i c l e s h a p e s , i m p l y t h a tt h e l a r g e r p a r t i c l e s c o m p o s e a maximum o f =85% o f t h em a g n e t i t e . U s i n g t h i s d i s t r i b u t i o n d a t a , w e e s t i m a t e t h a t b r a i nt i s s u e s c o nt ai n a m i n i m u m o f - 5 m i l l i o n c r y s t a l s p e r g r a m ,d i s t r i b u t e d i n 5 0 , 0 0 0 - 1 0 0 , 0 0 0 d i s c r e t e c l u s t e r s . S i m i l a r l y , t h em e n i n g e s c o n t a i n a m i n i m u m o f 1 0 0 m i l l i o n c r y s t a l s p e r g r a m ,i n 1 - 2 m i l l i o n c l u s t e r s .
E n e r g y - d i s p e r s i v e x - r a y a n a l y s e s o f t h e c r y s t a l s g a v e c o n -
s i s t e n t p e ak s o f F e , w i t h v a r i a b l e Cu p e a k s ( f r o m t h e c o p p e rTEM g r i d s ) a n d m i n o r S i , C a , a n d C l ( p r o b a b l y c o n t a m i n a n t sf r o m t h e g l a s s w a r e ) . M i x e d F e - T i o x i d e s , w h i c h a r e u s u a l l yp r e s e n t a t l e a s t i n t r a c e a m o u n t s i n g e o l o g i c a l l y f o r m e dm a g n e t i c m i n e r a l s , w e r e n o t d e t e c t e d i n a n y o f t h e b r a i nc r y s t a l s e x a m i n e d . I n d e x e d e l e c t r o n m i c r o d i f f r a c t i o n p a t -t e r n s f r o m i n d i v i d u a l c r y s t a l s a n d p a r t i c l e a g g r e g a t e s y i e l dt h e d - s p a c i n g s c h a r a c t e r i s t i c o f m a g n e t i t e ( F e 3 O 4 ) , w i t h
s m a l l e r p a r t i c l e s s h o w i n g v a r i a b l e o x i d a t i o n t o w a r d t h e f e r -r i m a g n e t i c s o l i d - s o l u t i o n e n d m e m b e r , m a g h e m i t e ( y - t F e 2 O 3 ) .T h i s o x i d a t i o n p r o b a b l y o c c u r r e d d u r i n g t h e e x t r a c t i o n p r o -
c e s s , a s i s o b s e r v e d c o m m o n l y i n v e r y f i n e g r a i n e d m a g n e -
t i t e s ( 2 2 ) .F i g . 2A i s a TEM i m a g e o f a c l u m p o f s m a l l p a r t i c l e s f r o m
t h e c e r e b e l l u m , a n d F i g . 2B s h o w s a h i g h - r e s o l u t i o n TEMi m a g e o f a w e l l - o r d er e d s i n g l e - d o m a i n m a g h e m i t e c r y s t a li m a g e d i n t h e [ 2 1 1 ] z o n e . I t d i s p l a y s s e v e r a l i n t e r s e c t i n g s e t so f c r y s t a l l a t t i c e f r i n g e s t h a t a p p e a r a s f i n e s t r i p e s t h a t r u n
a c r o s s t h e i m a g e ( a n d a r e v i e w e d b e s t a t a l o w a n g l e r e l a t i v et o t h e p a g e ) . T h e m o s t p r o m i n e n t s e t , w h i c h r u n s a c r o s s t h ew i d t h o f t h e c r y s t a l , c o r r e s p o n d s t o t h e 4 . 8 5 - A s p a c i n g o f t h e{ 1 1 1 } p l a n e ; a n o t h e r s e t p e r p e n d i c u l a r t o t h i s , r u n n i n g t h e
l e n g t h o f t h e c r y s t a l , h a s t h e 2 . 9 5 - A s p a c i n g o f t h e { 0 2 2 }p l a n e s . N o t e t h a t t h e [ 1 1 1 ] d i r e c t i o n o f t h e c r y s t a l , w h i c h i st h e e a s y d i r e c t i o n o f m a g n e t i z a t i o n ( 2 2 ) , i s p a r a l l e l t o t h ep a r t i c l e l e n g t h a n d t h a t t h e { 1 1 1 } f r i n g e s g o c o m p l e t e l y a c r o s s
t h e w i d t h o f t h e p a r t i c l e w i t h o u t d i s r u p t i o n . A s u p e r i m p o s e d
" g r a i n i n e s s " i s p r e s e n t , a l o n g w i t h s o m e w h a t i l l - d e f i n e de d g e s . T h e s e a r e t y p i c a l f e a t u r e s o f m a g n e t i t e c r y s t a l sf o r m e d w i t h i n m a g n e t o s o m e m e m b r a n e s ( 2 6 , 2 7 ) a n d a r e v e r ys i m i l a r t o t h e s i n g l e - d o m a i n p a r t i c l e s i n t h e m a g n e t o s o m ec h a i n s t r u c t u r e s p r e s e n t i n t h e d e r m e t h m o i d t i s s u e s o f
s a l m o n ( 1 5 ) . F i g . 2C s h o w s t h e i n d e x e d e l e c t r o n - d i f f r a c t i o ns p o t p a t t e r n f r o m t h i s c r y s t a l .
F i g . 2D s h o w s o n e o f t h e l a r g e r p a r t i c l e s , w h i c h i s 2 0 0 n mi n s i z e . O t h e r p a r t i c l e s r a n g e u p t o 6 0 0 n m i n d i a m e t e r .E l e c t r o n m i c r o d i f f r a c t i o n i n d i c a t e s t h a t t h e s e p a r t i c l e s a r e
d o m i n a t e d b y a s i n g l e c r y s t a l , w i t h o c c a s i o n a l s m a l l e r p a r -t i c l e s a d h e r i n g t o t h e i r s u r f a c e . T h e i r m e a s u r e d s i z e a n d
s h a p e s p l a c e t h e m w i t h i n t h e s i n g l e - d o m a i n s t a b i l i t y f i e l d( 2 5 ) . T h e s e p a r t i c l e s h a v e m a g n e t i c o r i e n t a t i o n e n e r g i e s i nt h e g e o m a g n e t i c f i e l d 2 0 - 1 5 0 t i m e s h i g h e r t h a n t h e b a c k -
g r o u n d t h e r m a l e n e r g y k T .
DISCUSSION
R e s u l t s f r o m t h e s e s t u d i e s i n d i c a t e t h a t h u m a n b r a i n a n d
m e n i n g e s c o n t a i n t r a c e a m o u n t s o f f e r r o m a g n e t i c m a t e r i a l .T h e s e m a g n e t i c p a r t i c l e s i n t h e human b r a i n a r e d i f f u s e l y a n d
h o m o g e n e o u s l y d i s t r i b u t e d o v e r a l l c e r e b r a l l o b e s , t h e c e r -e b e l l u m , b a s a l g a n g l i a , a n d m i d b r a i n . T h e c o n s i s t e n c y o f o u r
m a g n e t i c p r o p e r t y d a t a f r o m p i e c e t o p i e c e o f b r a i n t i s s u e a n d
f r o m p i e c e t o p i e c e o f m e n i n g e s s u g g e s t s t h a t t h e o b s e r v e d
m o m e n t s w e r e n o t p r o d u c e d b y o c c a s i o n a l c o n t a m i n a t i o n
f r o m t h e e n v i r o n m e n t b u t w e r e i n s i t u f e r r o m a g n e t i c m a t e -
r i a l s d i s t r i b u t e d i n a t i s s u e - c h a r a c t e r i s t i c f a s h i o n . T h e m a g -n e t i c m a t e r i a l w a s i n t h e t i s s u e s p r i o r t o t h e c h e m i c a l
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l a b e l e d IRM a c q u i s i t i o n s h o w t h e r e l a t i v e m a g n e t i c moments r e -m a i n i n g i n t h e s a m p l e s a f t e r a b r i e f e x p o s u r e t o a m a g n e t i c p u l s e o f
t h e i n d i c a t e d s t r e n g t h . T h e t e n d e n c y o f t h e c u r v e s t o f l a t t e n a t h i g hf i e l d l e v e l s i s c h a r a c t e r i s t i c o f t h e m a g n e t i t e - m a g h e m i t e s o l i d s o l u -t i o n s e r i e s ; m o s t o t h er f e r r o m a g n e t i c i r o n m i n e r a l s s a t u r a t e i n f i e l d s>1 T . T h e c u r v e s l a b e l e d A f o f s I R M s h o w t h e p r o g r e s s i v e a l t e r -
n a t i n g - f i e l d d e m a g n e t i z a t i o n o f t h e s a t u r a t i o n I R M . T h e m a g n e t i cf i e l d v a l u e a t w h i c h t h e s e t w o c u r v e s c r o s s i s t h e b e s t m e a s u r e o f t h ea v e r a g e c o e r c i v i t y . T h e o r d i n a t e o f t h e i n t e r s e c t i o n p o i n t f o r n o n -
i n t e r a c t i n g p a r t i c l e s o c c u r s a t t h e 5 0 % o v a l u e ; a d e p r e s s i o n o r s h i f t i nt h i s p o s i t i o n i s a n i n d i c a t i o n o f p a r t i c l e c l u m p i n g e f f e c t s . ( B ) T h e
a c q u i s i t i o n o f ARM. T h e u p p e r c o n t r o l c u r v e s h o w s d a t a f r o m a
s a m p l e o f m a g n e t o t a c t i c b a c t e r i a i n w h i c h t h e m a g n e t i t e c r y s t a l s a r e
a l i g n e d i n l i n e a r c h a i n s a n d h a v e f e w i n t e r p a r t i c l e i n t e r a c t i o n s ,w h e r e a s t h e l o w e r c o n t r o l c u r v e i s f r o m a s a m p l e o f m a g n e t i t e f r o m
c h i t o n t e e t h , w h i c h a r e s i n g l e - d o m a i n c r y s t a l s b u t a r e h i g h l y i n t e r -a c t i n g . S o l i d s q u a r e s a r e d a t a f r o m p i a f r o m t h e f r o n t a l l o b e , w h e r e a s
t h e o p e n c i r c l e s s h o w d a t a f r o m t h e c e r e b e l l u m . s I R M , s a t u r a t e dI R M .
d i g e s t i o n s t e p s , w h i c h a r e o f t h e most c o n c e r n f o r p o t e n t i a lc o n t a m i n a t i o n . An e x t e r n a l i n o r g a n i c s o u r c e i s a l s o u n l i k e l y
b e c a u s e o f t h e l a c k o f p a r t i c l e s c o n t a i n i n g m i x e d F e - T io x i d e s , w h i c h a r e c o m m o n i n i g n e o u s a n d m e t a m o r p h i cm a g n e t i t e s . S u r f a c e t e x t u r e s a n d c r y s t a l l o g r a p h i c f e a t u r e sf o r t h e s m a l l e r p a r t i c l e s a r e r e m a r k a b l y s i m i l a r t o b i o g e n i cm a g n e t i t e s s t u d i e d i n b a c t e r i a ( 2 7 ) a n d f i s h ( 1 5 ) . T h e { 1 1 1 }c r y s t a l a l i g n m e n t h a s b e e n i n t e r p r e t e d a s a b i o l o g i c a l m e c h -
a n i s m f o r m a x i m i z i n g t h e m a g n e t i c mome nt p e r p a r t i c l e , a s
t h e { 1 1 1 } d i r e c t i o n y i e l d s - 3% h i g h e r s a t u r a t i o n m a g n e t i z a -t i o n s t h a n d o o t h e r d i r e c t i o n s ( 1 5 , 2 7 , 2 8 ) . T h i s p r i s m a t i cp a r t i c l e s h a p e i s a l s o uncommon i n g e o l o g i c a l m a g n e t i t ec r y s t a l s o f t h i s s i z e , w h i c h a r e u s u a l l y o c t a h e d r a . H e n c e ,t h e s e m a g n e t i t e c r y s t a l s p r o b a b l y f o r m w i t h i n h u m a n t i s s u e sb y a s i m i l a r b i o l o g i c a l l y c o n t r o l l e d p r o c e s s . U n f o r t u n a t e l y ,t h e t i s s u e d i g e s t i o n a n d e x t r a c t i o n p r o c e s s d e s t r o y s t h e
B i o p h y s i c s : K i r s c h v i n k e t a l .
8/8/2019 Magnetite in the body
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F I G . 2 . TEM i m a g e s a n d d i f f r a c t i o n p a t t e r n s o f r e p r e s e n t a t i v e m a g n e t i t e a n d m a g h e m i t e c r y s t a l s f r o m t h e h u m a n c e r e b e l l u m . ( A ) A c l u m p
o f s m a l l p a r t i c l e s . T h e h i g h - r e s o l u t i o nTEM
i m a g e o f t h e m a g h e m i t e c r y s t a l i n B s h o w s t h e p a t t e r n o f i n t e r s e c t i n g { 1 1 1 } a n d { O 2 2 } f t i n g e s , w i t hp a r t i c l e e l o n g a t i o n i n t h e [ 1 1 1 ] l a t t i c e d i r e c t i o n . ( C ) T h e i n d e x e d s e l e c t e d - a r e a e l e c t r o n d i f f r a c t i o n p a t t e r n o f t h i s c r y s t a l , t a k e n i n t h e ( 2 1 1 ) z o n e .
( A f e w m i s c e l l a n e o u s s p o t s a r e a l s o p r e s e n t f r o m t h e a d j a c e n t c r y s t a l s s e e n i n A , a n d t h e f a i n t r o w o f s p o t s m i d w a y b e t w e e n t h e b r i g h t r o w sa r e [ 0 1 1 ] a n d e q u i v a l e n t r e f l e c t i o n s t h a t i n d i c a t e t h e o x i d a t i o n t o m a g h e m i t e . ) T h e d i f f r a c t i o n r i n g s f r o m a n a g g r e g a t e o f s o W U l c r y s t a l s c o n f i r m st h e m a g n e t i t e - m a g h e m i t e i d e n t i f i c a t i o n . T h e s e m e a s u r e d v a l u e s / y - t F e 2 0 3 s t a n d a r d s / a n d [ i n d e x e d ] d - s p a c i n g s f o r t h e r i n g s a r e , r e s p e c t i v e l y , 4 . 0A / 4 . 1 8 A [ 2 0 0 ] , 4 . 8 A / 4 . 8 2 A [ 1 1 1 ] , 3 . 2 A / 3 . 4 1 A [ 2 1 1 ] , 2 . 8 A / 2 . 9 5 A [ 2 2 0 ] , 2 . 6 A / 2 . 7 8 A 1 2 2 1 ] , 2 . 2 A / 2 . 2 3 A [ 3 2 1 ] , 1 . 8 A / 1 . 8 7 A [ 4 2 0 ] , 1 . 7A / 1 . 7 0 A [ 4 2 2 ] , 1 . 5 A / 1 . 6 1 A [ 5 1 1 ] , a n d 1 . 3 A / 1 . 3 2 A [ 6 2 0 ] . T h e t e t r a g o n a l r e f l e c t i o n s [ 2 1 1 ] , [ 2 2 1 ] , a n d [ 3 2 1 ] a r e p r e s e n t i n m a g h e m i t e , a n d n o ti n m a g n e t i t e , a n d t h e p a t t e r n f r o m t h e a g g r e g a t e i s a m i x t u r e o f t h e t w o . O n e o f t h e l a r g e m a g n e t i t e p a r t i c l e s i s s h o w n i n D ( d i f f r a c t i o n p a t t e r nn o t s h o w n ) .
c e l l u l a r o r g a n i z a t i o n o f t h e p a r t i c l e s . O n l y t h e ARM r e s u l t sy i e l d c l u e s t o t h e i n s i t u g r o u p i n g i n s m a l l c l u m p s .
I n r e c e n t y e a r s , s e v e r a l m e d i c a l g r o u p s h a v e c l a i m e d t h a tMRI i m a g e s w e i g h t e d b y T 1 a n d T 2 v a l u e s c o r r e l a t e d w i t h t h eo b s e r v e d d i s t r i b u t i o n o f s t a i n a b l e f e r r i c i r o n i n human b r a i nt i s s u e ( 2 , 2 9 , 3 0 ) . T h e s e a n o m a l o u s v a l u e s h a v e b e e n i n t e r -
p r e t e d a s a r i s i n g f r o m i r r e g u l a r d i s t r i b u t i o n s o f par anetici r o n ( d e o x y h e m o g l o b i n , f e r r i t i n , a n d h e m o s i d e r i n ) . I r o n d i s -t r i b u t i o n s m e a s u r e d i n t h i s f a s h i o n i n c r e a s e d w i t h a g e , a s i sk n o w n f r o m e x t e n s i v e h i s t o l o g i c a l w o r k ( 2 4 ) . H o w e v e r , t h i si n t e r p r e t a t i o n w a s c h a l l e n g e d s u b s e q u e n t l y b y C h e n e t a l .( 3 1 ) , who f o u n d g e n e r a l l y p o o r c o r r e l a t i o n b e t w e e n i r o n
P r o c . N a d . A c a d . S c i . USA 8 9 ( 1 9 9 2 )
8/8/2019 Magnetite in the body
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P r o c . N a t l . A c a d . S c i . USA 8 9 ( 1 9 9 2 ) 7 6 8 7
c o n c e n t r a t i o n a n d T 2 r e l a x a t i o n , a n d b y B i z z i e t a l . ( 3 2 ) , whod i s c o v e r e d t h a t t h e i r o n - c o r r e l a t e d s p i n e c h o e f f e c t s d i d n o t
h a v e t h e q u a d r a t i c v a r i a t i o n w i t h i n c r e a s i n g m a g n e t i c f i e l ds t r e n g t h p r e d i c t e d b y t h e p a r a m a g n e t i c h y p o t h e s i s . A l l o f
t h e s e r e s u l t s a r e m o r e c o m p a t i b l e w i t h t h e p r e s e n c e o f t r a c el e v e l s o f m a g n e t i t e .
T h e p r e s en c e o f m a g n e t i t e i n human t i s s u e s h a s p o t e n t i a li m p l i c a t i o n s f o r a t l e a s t t w o b i o m e d i c a l i s s u e s t h a t h a v e b e e n
d i s c u s s e d e x t e n s i v e l y i n t h e l i t e r a t u r e ; t h e se i n c l u de human
e x p o s u r e t o t h e s t r o n g s t a t i c f i e l d s u s e d i n MR I s t u d i e s ( 3 )a n d t h e much w e a k e r 5 0 - a n d 6 0 - H z f i e l d s p r o d u c e d b y t h ee l e c t r i c p o w e r s y s t e m a n d a p p l i a n c e s i n i n d u s t r i a l i z e d c o u n -
t r i e s ( 4 - 7 ) . ( i ) MRI s y s t e m s a r e now b e i n g u s e d r o u t i n e l y i nc l i n i c a l a p p l i c a t i o n s t h a t s u b j e c t p a t i e n t s t o s t a t i c b a c k g r o u n dm a g n e t i c f i e l d s i n e x c e s s o f 1 . 5 T , 3 0 , 0 00 t i m es s t r o n g e r t h a n
t y p i c a l g e o m a g n e t i c f i e l d s . U n d e r t h e s e c o n d i t i o n s t h e m a x -imum m a g n e t o s t a t i c o r i e n t a t i o n a l p o t e n t i a l e n e r g i e s f o r t h e
m a g n e t i c p a r t i c l e c l u m p s a r e b e t w e e n 1 0 3 a n d 1 0 7 t i m e s
h i g h e r t h a n t h e t h e r m a l e n e r g y k T a t b o d y t e m p e r a t u r e .
H e n c e , t h e e n e r g i e s a r e much l a r g e r t h a n t h e c h e m i c a l
e n e r g i e s p r e s e n t i n c o v a l e n t b o n d s , w h i c h t y p i c a l l y a r e o n t h eo r de r o f 1 0 0 k T . ( i i ) T h e m a g n e t i c t o r q u e f r o m e x t e r n a la l t e r n a t i n g f i e l d s w i l l i n d u c e m e c h a n i c a l o s c i l l a t i o n s i n t h ep a r t i c l e s , a n d t h e p o t e n t i a l e x i s t s f o r s u c h m o t i o n s t o h a v e
e f f e c t s l i k eo p e n i n g t r a n s m e m b r a n e i o n c h a nn el s . T w o
s e p -a r a t e a n a l y t i c a l a p p r o a c h e s s u g g e s t t h a t f i e l d s o f 5 0 o r 6 0 Hzw i t h p e a k i n t e n s i t i e s s l i g h t l y s t r o n g e r t h a n t h a t o f t h e e a r t hw o u l d b e r e q u i r e d t o make t h e s e e f f e c t s s t a n d a b o v e k T ( 7 ,3 3 ) , b u t t h e l a r g e n u m b e r s o f c r y s t a l s m i g h t a l l o w a v e r a g i n gt o y i e l d e f f e c t s a t l o w e r l e v e l s . A l t h o u g h p e a k a l t e r n a t i n gm a g n e t i c f i e l d s g e n e r a t e d b y m o s t e l e c t r i c t r a n s m i s s i o n l i n e sa r e w e l l b e l o w t h i s l e v e l , s o m e e l e c t r i c a p p l i a n c e s p r o d u c es t r o n g e r f i e l d s ( 3 4 ) . U n f o r t u n a t e l y , w i t h o u t m o r e k n o w l e d g eo f t h e c e l l u l a r l o c a t i o n , u l t r a s t r u c t u r e , o r b i o l o g i c a l f u n c t i o n
o f t h e s e p a r t i c l e s , i t i s i m p o s s i b l e t o p r e d i c t w h e t h e r m a g -n e t o m e c h a n i c a l e f f e c t s o f t h i s s o r t p o s e a human h e a l t hh a z a r d .
W e t h a n k D r . C a r o l M i l l e r o f t h e U n i v e r s i t y o f S o u t h e r n C a l i f o r n i aM e d i c a l S c h o o l f o r p r o v i d i n g a c c e s s t o b r a i n m a t e r i a l s , D r s . J u a n
D i a z - R i c c i , D e r e k H . F e n d e r , a n d L e o n T . S i l v e r f o r h e l p f u l s u p p o r ta n d d i s c u s s i o n s , a n d D r . C . C . P a t t e r s o n f o r u l t r a p u r e w a t e r . D r .
B r e n t F u l t z a n d M s . C a r o l G a r l a n d o f t h e C a l t e c h M a t e r i a l s R e s e a r c hC e n t e r p r o v i d e d e s s e n t i a l h e l p w i t h t h e h i g h - v o l t a g e e l e c t r o n m i -c r o s c o p y . D r s . K . M. Towe a n d R . B . F r a n k e l p r o v i d e d c r i t i c a l a n du s e f u l r e v ie w s o f t h e m a n u s c r i p t . T h i s w o r k w a s s u p p o r t e d b yN a t i o n a l I n s t i t u t e s o f H ea l t h G r a n t G M - 4 1 6 3 5 , a n d t h e C a l t e c h
M a t e r i a l s R e s e a r c h F a c i l i t y i s s u p p o r t e d b y N a t i o n a l S c i e n c e F o u n -
d a t i o n G r a n t D M R - 8 8 1 1 7 9 5 . T h i s i s c o n t r i b u t i o n 5 0 6 8 f r o m t h eD i v i s i o n o f G e o l o g i c a l a n d P l a n e t a r y S c i e n c e s o f t h e C a l i f o r n i aI n s t i t u t e o f T e c h n o l o g y .
1 . B r i t t e n h a m , G . M . , F a r r e l l , D . E . , H a r r i s , J . W . , F e l d m a n ,E . S . , D a n i s h , E . H . , M u i r , W. A . , T r i p p , J . H . & B e l l o n ,E . M. ( 1 9 8 2 ) N . E n g l . J . M e d . 3 0 7 , 1 6 7 1 - 1 6 7 5 .
2 . G o m o r i , J . M . , G r o s s m a n , R . I . , G o l d b e r g , H . I . , Z i m m e r m a n ,R . A . & B i l a n i u k , L . T . ( 1 9 8 5 ) R a d i o l o g y 1 5 7 , 8 7 - 9 3 .
3 . T e n f o r d e , T . S . & B u d i n g e r , T . F . ( 1 9 8 6 ) i n NMR i n M e d i c i n e :I n s t r u m e n t a t i o n a n d C l i n i c a l A p p l i c a t i o n s , e d s . T h o m a s , S . R .
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