h - simps ( 1.6 m diameter ) were fabricated as in 8 , 14 .
d - simps ( 1.0 m diameter , 400 nm thickness ) were fabricated by newly developed protocols . briefly , heavily doped p++ type ( 100 ) silicon wafers with resistivity of 0.005 ohm - cm ( silicon quest , inc , santa clara , ca ) were used as the silicon source . a 400
nm porosity layer was formed by applying a 7ma / cm current for 125  in a 1:3 hf(49%):ethanol solution .
the electrical current was then increased to 76ma / cm and applied for 8  forming a high porosity release layer .
a 40 nm sio2 layer was deposited by low pressure chemical vapor deposition at 400c .
standard photolithography was used to pattern a 1.0 m circular pattern with 1.0 m pitch over the sio2 capped porous layer using a contact aligner ( k.suss ma6 mask aligner ) and nr9 - 500p photoresist ( futurrex franklin , nj , usa ) . the pattern was transferred into the porous double layer by dry etch in cf4 plasma ( plasmatherm 790 , 25sccm cf4 , 100 mtorr , 200w rf ) .
the capping sio2 layer was removed in 49% hf , and the particles were released from the substrate by sonication in isopropanol .
the particles were treated with h2o2 at 100c to oxidize the surface . volumetric particle size
, size distribution and count were obtained using a multisizer 4 coulter particle counter ( beckman coulter , fullerton , ca , usa ) .
the simp zeta potential was analyzed in phosphate buffer ( pb , ph 7.3 ) using a zetapals ( brookhaven instruments corporation , holtsville , ny , usa ) .
polyhydroxylated gadofullerenes [ gd@c60(oh)x ; x ~27 ] were prepared9 , 22 and dissolved in hplc grade water .
the resulting solution was passed through a 0.2  filter and centrifuged at 3200 rpm for 10 minutes .
individual us - tubes loaded with gd ions were prepared as described previously.11 , 13 , 36 as produced , individual gadonanotubes ( gnts ) were then dispersed in a biocompatible , non - ionic , pluronic ( polyethylene oxide - polypropylene oxide block copolymer , basf corporation , nj ) polymer ( 1.0 % w / v ) .
the dispersion was centrifuged at 3200 rpm for 10 minutes and the supernatant was dialyzed against running water to remove any excess surfactant .
simps were lyophilized to dryness for 6 hours in non - stick plastic tubes using labconco freezone freeze dryer system .
two protocols were tested : ( 1 ) single - step and ( 2 ) sequential loading . for ( 1 ) , dry si particles were mixed with 300 l of gd - cas solution .
the resulting suspension was sonicated ( 30 w bath sonicator ) for 5 minutes and centrifuged for 10 min at 3200 rpm .
the supernatant was discarded and the sediment washed twice with deionized water to remove any excess of gd - cas adhering to the outer surface of the si particles . for ( 2 ) , the si particles were introduced initially to 100 l of gd - cas stock solutions , followed by sonication and centrifugation . after the supernatant was discarded , another 100 l of the stock solution was added followed by sonication and centrifugation .
the process was repeated with addition of 100 l of stock solution followed by loading and washing twice with di water . in order to estimate the efficiency of loading ,
si and gd ions released from the particles during the degradation process were measured using a perkin - elmer elan 9000 inductively coupled plasma - optical emission spectrometer ( icp - oes ) respectively .
the nanoconstructs were then dispersed in hplc water and left at room temperature . at 2 h and 24 h ,
the simps were filter - spun using 0.45 m filter columns at 3200 rpm for 5 min .
the washings were assessed for the concentration of gd - ions using icp - oes .
the 1/t1 nmrd profiles of debundled gnts were obtained at 310.0 k on a stelar spinmaster fast field - cycling relaxometer ; bruker minispecs ( 30 , 40 and 60 mhz ) ; and bruker spectrometers ( 100 , 200 and 400 mhz ) .
t1 relaxation times of gnts in nanoporous silicon particles were measured in a spin track bench top relaxometer ( process nmr associates , ct ) operating at 60 mhz and 37 c with a 5 mm probe .
t1 relaxation times were measured using inversion recovery sequence and hplc grade water was used as diamagnetic control .
phantom studies in clinical scanner were performed in a 1.5 t commercial scanner ( achieva , philips medical systems , best , the netherlands ) equipped with a 32-channel radiofrequency system .
a 32- or 16-element phased - array surface coil was used for mr signal reception .
an inversion recovery sequence was used for image acquisition with tr = 7500 ms and te = 20 ms .
 magnetic resonance imaging contrast agents are currently designed by modifying their structural and physiochemical properties in order to improve relaxivity and to enhance image contrast . here 
 we show a general method for increasing relaxivity by confining contrast agents inside the nanoporous structure of silicon particles . 
 magnevist , gadofullerenes and gadonanotubes were loaded inside the pores of quasi - hemispherical and discoidal particles . for all combinations of nanoconstructs , a boost in longitudinal proton relaxivity r1 was observed : for magnevist , r1~14 mm-1s-1/gd3+ion ( ~8.1510 + 7 mm-1s-1/construct ) ; for gadofullerenes , r1~200 mm-1s-1/gd3+ion ( ~710 + 9 mm-1s-1/construct ) ; for gadonanotubes , r1~150 mm-1s-1/gd3+ion ( ~210 + 9 mm-1s-1/construct ) . 
 these relaxivity values are about 4 to 50 times larger than that of clinically - available gadolinium - based agents ( ~4 mm-1s-1 /gd3+ion ) . 
 the enhancement in contrast is attributed to the geometrical confinement of the agents , which influences the paramagnetic behavior of the gd3+ions . 
 thus , nanoscale confinement offers a new and general strategy for enhancing the contrast of gadolinium - based contrast agents . 
Supplementary Material
Fabrication, modification and characterization of the SiMPs
Fabrication and modification of GFs and GNTs
Loading of the SiMPs with Gd-CAs
Release of GNTs from SiMPs
Relaxometry studies