<i>Objectives</i>. Bone ischemia and necrosis are challenging to treat, requiring investigation of native and engineered bone revascularisation processes through advanced imaging techniques. This study demonstrates an experimental two-step method for precise bone and vessel analysis in native bones or vascularised bone grafts using X-ray microtomography (<i>&#x3bc;</i>CT), without interfering with further histological processing.<i> Methods</i>. Distally ligated epigastric arteries or veins of 6 nude rats were inserted in central channels of porous hydroxyapatite cylinders and these pedicled grafts were implanted subcutaneously. One week later, the rats were perfused with ink-gelatin and euthanised and the femurs, tibias, and grafts were explanted. Samples were scanned using <i>&#x3bc;</i>CT, decalcified, incubated with phosphotungstic acid (PTA) for contrast enhancement, rescanned, and processed histologically.<i> Results.</i> Contrast-enhanced <i>&#x3bc;</i>CT displayed the course and branching of native bone vessels. Histologically, both central (&#x2212;17&#x25;) and epiphyseal vessels (&#x2212;58&#x25;) appeared smaller than in <i>&#x3bc;</i>CT scans. Hydroxyapatite cylinders were thoroughly vascularised but did not display bone formation. Grafts with a central artery had more (+58&#x25;) and smaller (&#x2212;52&#x25;) vessel branches compared to grafts with a vein.<i> Conclusions</i>. We present a relatively inexpensive and easy-to-perform two-step method to analyse bone and vessels by <i>&#x3bc;</i>CT, suitable to assess a variety of bone-regenerative strategies.

Sarah Sutter

Atanas Todorov

Tarek Ismail

Alexander Haumer

Ilario Fulco

Georg Schulz

Arnaud Scherberich

Alexandre Kaempfen

Ivan Martin

Dirk J. Schaefer

Contrast-Enhanced Microtomographic Characterisation of Vessels in Native Bone and Engineered Vascularised Grafts Using Ink-Gelatin Perfusion and Phosphotungstic Acid

<i>Objective.</i> To provide a clinically relevant overview of the analytical interference by contrast agents (CA) in laboratory blood test measurements.<i> Materials and Methods.</i> The effects of five CAs, gadobutrol, gadoterate meglumine, gadoxetate disodium, iodixanol, and iomeprol, were studied on the 29 most frequently performed biochemical assays. One-day-old plasma, serum, and whole blood were spiked with doses of each agent such that the gadolinium agents and the iodine agents reached concentrations of 0.5 mM and 12 mg iodine/mL, respectively. Subsequently, 12 assays were reexamined using <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-2.15067pt" id="M1" height="11.439pt" version="1.1" viewBox="-0.0498162 -9.28833 18.0025 11.439" width="18.0025pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><path id="g113-48" d="M368 703H309L44 -163H104L368 703Z"/></g><g transform="matrix(.013,0,0,-0.013,11.601,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g></svg> and <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-2.15067pt" id="M2" height="11.439pt" version="1.1" viewBox="-0.0498162 -9.28833 18.0025 11.439" width="18.0025pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><use xlink:href="#g113-48"/></g><g transform="matrix(.013,0,0,-0.013,11.601,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g></svg> of these CA concentrations. The results were assessed statistically by a paired Student’s <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063999pt" id="M3" height="8.02022pt" version="1.1" viewBox="-0.0498162 -7.81382 4.54925 8.02022" width="4.54925pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-117" d="M324 430H196L233 583L223 592L145 529L120 430H54L29 396L31 388H111L56 126C33 15 54 -12 77 -12C137 -12 214 57 250 95L233 119C208 92 155 59 138 59C126 59 120 70 131 125L186 390L298 394L324 430Z"/></g></svg>-test.<i> Results.</i> Iodixanol produced a negative interference on the bicarbonate (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M4" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 50.7895 11.7782" width="50.7895pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-113" d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-50"/></g></svg>), lactate dehydrogenase (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M5" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 57.0529 11.7782" width="57.0529pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><use xlink:href="#g113-50"/></g></svg>), and zinc (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M6" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 57.0529 11.7782" width="57.0529pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><use xlink:href="#g113-53"/></g></svg>) assays and a positive interference on the albumin (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M7" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 57.0529 11.7782" width="57.0529pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><path id="g113-55" d="M137 343C167 482 260 545 321 574C357 591 397 603 429 609L423 641C382 634 335 622 295 608C189 570 37 457 37 238C37 84 125 -12 242 -12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><use xlink:href="#g113-51"/></g></svg>), calcium (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M8" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 57.0529 11.7782" width="57.0529pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-91"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><use xlink:href="#g113-50"/></g></svg>), ionized calcium (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M9" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 57.0529 11.7782" width="57.0529pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><path id="g113-57" d="M249 635C141 635 70 555 70 471C70 401 114 353 179 316C143 294 106 267 90 252C68 231 45 202 45 157C45 50 130 -12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><use xlink:href="#g113-55"/></g></svg>), iron (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M10" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 57.0529 11.7782" width="57.0529pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-91"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><use xlink:href="#g113-50"/></g></svg>), and potassium (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M11" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 57.0529 11.7782" width="57.0529pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><use xlink:href="#g113-52"/></g></svg>) assays. Iomeprol produced a negative interference on the bicarbonate (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M12" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 57.0529 11.7782" width="57.0529pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><path id="g113-56" d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"/></g></svg>) and magnesium (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M13" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 57.0529 11.7782" width="57.0529pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><use xlink:href="#g113-50"/></g></svg>) assays and a positive interference on the calcium (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M14" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 57.0529 11.7782" width="57.0529pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-91"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><use xlink:href="#g113-50"/></g></svg>) and potassium (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M15" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 57.0529 11.7782" width="57.0529pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><use xlink:href="#g113-51"/></g></svg>) assays. Gadoxetate disodium produced a negative interference on the iron (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M16" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 57.0529 11.7782" width="57.0529pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-91"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><use xlink:href="#g113-50"/></g></svg>) and zinc (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M17" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 57.0529 11.7782" width="57.0529pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-91"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><use xlink:href="#g113-50"/></g></svg>) assays and a positive interference on the sodium (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M18" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 50.7895 11.7782" width="50.7895pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-52"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-51"/></g></svg>) assay.<i> Conclusion.</i> CAs cause analytical interference. Attention should be given to the above-mentioned analyte-CA combinations when assessing laboratory blood test results obtained after CA administration.

Sigrid Otnes

Niels Fogh-Andersen

Janne R&#xf8;msing

Henrik S. Thomsen

Analytical Interference by Contrast Agents in Biochemical Assays

Molecular magnetic resonance imaging targeted to an endothelial integrin involved in neoangiogenesis was compared to DCE-US and immunochemistry to assess the early response of three different therapeutic agents in renal cell carcinoma. Human A498 renal cells carcinoma was subcutaneously inoculated into 24 nude mice. Mice received either phosphate-buffered saline solution, sunitinib, everolimus, or bevacizumab during 4 days. DCE-US and molecular MRI targeting <i>α</i>v<i>β</i>3 were performed at baseline and 4 days after treatment initiation. PI, AUC, relaxation rate variations <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063999pt" id="M1" height="10.3089pt" version="1.1" viewBox="-0.0498162 -10.1025 28.9879 10.3089" width="28.9879pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-133" d="M600 0V24L339 665L311 657L43 24V0H600ZM497 50H107L303 539L497 50Z"/></g><g transform="matrix(.013,0,0,-0.013,8.327,0)"><path id="g113-83" d="M610 18C585 26 567 34 540 68C517 97 499 128 476 171C452 215 425 276 413 304C496 332 570 394 570 494C570 555 545 595 509 619S419 650 364 650H139L133 622C216 615 219 612 203 527L129 132C112 40 105 36 23 28L17 0H279L285 28C199 34 194 40 211 132L239 284H284C320 284 334 275 351 236C374 182 394 140 420 93C459 23 495 -1 592 -8H600L610 18ZM480 485C480 424 449 372 403 342C374 323 338 316 293 316H245L291 562C296 589 301 601 311 608S337 618 358 618C432 618 480 575 480 485Z"/></g><g transform="matrix(.013,0,0,-0.013,16.478,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g><g transform="matrix(.0091,0,0,-0.0091,22.809,-5.741)"><path id="g50-43" d="M486 158C486 177 478 202 466 220C413 228 386 236 336 262C386 288 413 297 466 304C478 323 486 347 485 366C470 376 444 381 422 380C389 338 368 319 321 288C323 345 329 372 349 422C339 442 322 461 305 470C289 461 271 442 262 422C281 372 287 345 290 288C243 319 222 338 189 380C167 381 142 376 125 366C125 347 133 322 145 304C198 296 225 288 275 262C225 236 198 227 145 220C133 201 125 177 126 158C141 148 167 143 189 144C222 186 243 205 290 236C288 179 282 152 262 102C272 82 289 63 306 54C322 63 340 82 350 102C330 152 324 179 321 236C368 205 390 186 422 144C444 143 470 148 486 158Z"/></g></svg>, and percentage of vessels area quantified on CD31-stained microvessels were compared. Significant decreases were observed for PI and AUC parameters measured by DCE-US for bevacizumab group as early as 4 days, whereas molecular <i>α</i>v<i>β</i>3-targeted MRI was able to detect significant changes in both bevacizumab and everolimus groups. Percentage of CD31-stained microvessels was significantly correlated with DCE-US parameters, PI (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2064009pt" id="M2" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 44.9698 8.8423" width="44.9698pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-83"/></g><g transform="matrix(.013,0,0,-0.013,11.783,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g><g transform="matrix(.013,0,0,-0.013,23.046,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,29.286,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g 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transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-113" d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g></svg>) and AUC (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2064009pt" id="M4" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 44.9698 8.8423" width="44.9698pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-83"/></g><g transform="matrix(.013,0,0,-0.013,11.783,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,23.046,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.286,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.25,0)"><use xlink:href="#g113-57"/></g><g transform="matrix(.013,0,0,-0.013,38.49,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M5" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 57.0529 11.7782" width="57.0529pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><use xlink:href="#g113-52"/></g></svg>). The percentage of vessel tissue area was significantly reduced (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M6" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 44.5261 11.7782" width="44.5261pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-50"/></g></svg>) in both sunitinib and bevacizumab groups. We report an early detection of neoangiogenesis modification after induction of targeted therapies, using DCE-US or <i>α</i>v<i>β</i>3-targeted MRI. We consider these outcomes should encourage clinical trial developments to further evaluate the potential of this molecular MRI technique.

Ingrid Leguerney

Ludovic de Rochefort

Marie Poirier-Quinot

Alexandre Ingels

Xavier Violas

Sandra Robin

Paule Opolon

Rose-Marie Dubuisson

St&#xe9;phanie Pitre-Champagnat

Philippe Robert

Nathalie Lassau

Molecular Imaging to Predict Response to Targeted Therapies in Renal Cell Carcinoma

Gliomas possess complex and heterogeneous vasculatures with abnormal hemodynamics. Despite considerable advances in diagnostic and therapeutic techniques for improving tumor management and patient care in recent years, the prognosis of malignant gliomas remains dismal. Perfusion-weighted magnetic resonance imaging techniques that could noninvasively provide superior information on vascular functionality have attracted much attention for evaluating brain tumors. However, nonconsensus imaging protocols and postprocessing analysis among different institutions impede their integration into standard-of-care imaging in clinic. And there have been very few studies providing a comprehensive evidence-based and systematic summary. This review first outlines the status of glioma theranostics and tumor-associated vascular pathology and then presents an overview of the principles of dynamic contrast-enhanced MRI (DCE-MRI) and dynamic susceptibility contrast-MRI (DSC-MRI), with emphasis on their recent clinical applications in gliomas including tumor grading, identification of molecular characteristics, differentiation of glioma from other brain tumors, treatment response assessment, and predicting prognosis. Current challenges and future perspectives are also highlighted.

Junfeng Zhang

Heng Liu

Haipeng Tong

Sumei Wang

Yizeng Yang

Gang Liu

Weiguo Zhang

Clinical Applications of Contrast-Enhanced Perfusion MRI Techniques in Gliomas: Recent Advances and Current Challenges

Imaging using affibody molecules enables discrimination between breast cancer metastases with high and low expression of HER2, making appropriate therapy selection possible. This study aimed to evaluate if the longer half-life of <sup>64</sup>Cu (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-4.67948pt" id="M1" height="13.6416pt" version="1.1" viewBox="-0.0498162 -8.96212 20.6158 13.6416" width="20.6158pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-85" d="M620 675H597C578 656 570 650 541 650H144C112 650 104 653 94 675H72C59 618 42 552 23 493L53 491C71 534 88 564 105 585C124 608 144 615 238 615H290L197 121C182 40 174 34 88 28L82 0H361L367 28C275 34 266 38 281 121L374 615H441C522 615 543 608 553 583C562 560 566 531 565 493L597 494C603 551 612 629 620 675Z"/></g><g transform="matrix(.0091,0,0,-0.0091,7.176,3.132)"><path id="g50-50" d="M389 0V32C297 38 291 46 291 118V635C234 613 175 595 109 583V556L161 554C203 552 207 547 207 497V118C207 46 201 38 110 32V0H389Z"/></g><g transform="matrix(.0091,0,0,-0.0091,11.608,3.132)"><path id="g50-48" d="M381 704H317L48 -163H112L381 704Z"/></g><g transform="matrix(.0091,0,0,-0.0091,15.515,3.132)"><path id="g50-51" d="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z"/></g></svg> = 12.7 h) would make <sup>64</sup>Cu a superior nuclide compared to <sup>68</sup>Ga for PET imaging of HER2 expression using affibody molecules. The synthetic ZHER2:S1 affibody molecule was conjugated with the chelators NOTA or NODAGA and labeled with <sup>64</sup>Cu. The tumor-targeting properties of <sup>64</sup>Cu-NOTA-ZHER2:S1 and <sup>64</sup>Cu-NODAGA-ZHER2:S1 were evaluated and compared with the targeting properties of <sup>68</sup>Ga-NODAGA-ZHER2:S1 in mice. Both <sup>64</sup>Cu-NOTA-ZHER2:S1 and <sup>64</sup>Cu-NODAGA-ZHER2:S1 demonstrated specific targeting of HER2-expressing xenografts. At 2 h after injection of <sup>64</sup>Cu-NOTA-ZHER2:S1, <sup>64</sup>Cu-NODAGA-ZHER2:S1, and <sup>68</sup>Ga-NODAGA-ZHER2:S1, tumor uptakes did not differ significantly. Renal uptake of <sup>64</sup>Cu-labeled conjugates was dramatically reduced at 6 and 24 h after injection. Notably, radioactivity uptake concomitantly increased in blood, lung, liver, spleen, and intestines, which resulted in decreased tumor-to-organ ratios compared to 2 h postinjection. Organ uptake was lower for <sup>64</sup>Cu-NODAGA-ZHER2:S1. The most probable explanation for this biodistribution pattern was the release and redistribution of renal radiometabolites. In conclusion, monoamide derivatives of NOTA and NODAGA may be suboptimal chelators for radiocopper labeling of anti-HER2 affibody molecules and, possibly, other scaffold proteins with high renal uptake. 

Vladimir Tolmachev

Cheng-Bin Yim

Johan Rajander

Anna Perols

Amelie Eriksson Karlstr&#xf6;m

Merja Haaparanta-Solin

Tove J. Gr&#xf6;nroos

Olof Solin

Anna Orlova

Comparative Evaluation of Anti-HER2 Affibody Molecules Labeled with <sup>64</sup>Cu Using NOTA and NODAGA

The objective of this meta-analysis is to explore the correlation between the apparent diffusion coefficient (ADC) on diffusion-weighted MR and the standard uptake value (SUV) of <sup>18</sup>F-FDG on PET/CT in patients with cancer. Databases such as PubMed (MEDLINE included), EMBASE, and Cochrane Database of Systematic Review were searched for relevant original articles that explored the correlation between SUV and ADC in English. After applying Fisher’s <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063904pt" id="M1" height="6.1673pt" version="1.1" viewBox="-0.0498162 -5.96091 5.60619 6.1673" width="5.60619pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-115" d="M393 379C402 394 400 411 393 422C384 437 365 448 348 448C301 448 237 372 186 285H182L193 335C210 408 205 448 178 448C150 448 80 402 29 344L45 321C80 355 114 373 122 373C128 373 130 365 124 330C106 228 76 98 50 -5L57 -12C82 -5 112 3 132 6L172 203C196 256 234 304 254 329C275 355 293 367 306 367C318 367 330 360 342 348C347 343 355 343 365 350S386 367 393 379Z"/></g></svg>-to-<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.29774pt" id="M2" height="6.44133pt" version="1.1" viewBox="-0.0498162 -6.14359 6.59789 6.44133" width="6.59789pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-123" d="M475 445L452 468C423 436 401 426 385 426S352 427 305 436C268 443 216 448 185 448C156 448 128 425 102 382C89 360 77 338 64 304L89 291C117 340 143 380 190 380C214 380 268 376 295 373C320 370 344 371 362 374L70 101C32 65 23 36 23 18C23 5 27 -3 31 -8C36 -8 39 -6 42 -1C52 15 67 31 80 40S110 49 143 33C195 8 257 -20 290 -20C339 -20 382 11 439 129L416 148C366 74 334 55 305 55C278 55 236 68 203 81C169 94 141 100 122 96C205 170 348 308 411 376L475 445Z"/></g></svg> transformation, correlation coefficient (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063904pt" id="M3" height="6.1673pt" version="1.1" viewBox="-0.0498162 -5.96091 5.60619 6.1673" width="5.60619pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-115"/></g></svg>) values were extracted from each study and 95% confidence intervals (CIs) were calculated. Sensitivity and subgroup analyses based on tumor type were performed to investigate the potential heterogeneity. Forty-nine studies were eligible for the meta-analysis, comprising 1927 patients. Pooled <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063904pt" id="M4" height="6.1673pt" version="1.1" viewBox="-0.0498162 -5.96091 5.60619 6.1673" width="5.60619pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-115"/></g></svg> for all studies was −0.35 (95% CI: −0.42–0.28) and exhibited a notable heterogeneity (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.04979992pt" id="M5" height="11.6412pt" version="1.1" viewBox="-0.0498162 -11.5914 10.6309 11.6412" width="10.6309pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-74" d="M405 650H141L135 622C222 616 230 610 215 535L133 116C118 41 113 33 29 28L23 0H289L295 28C209 33 205 40 219 116L298 535C312 609 317 616 399 622L405 650Z"/></g><g transform="matrix(.0091,0,0,-0.0091,5.567,-5.741)"><path id="g50-51" d="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z"/></g></svg> = 78.4%; <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.0498209pt" id="M6" height="8.68572pt" version="1.1" viewBox="-0.0498162 -8.6359 8.15071 8.68572" width="8.15071pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g></svg> &lt; 0.01). In terms of the cancer type subgroup analysis, combined correlation coefficients of ADC/SUV range from −0.12 (lymphoma, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063904pt" id="M7" height="6.1673pt" version="1.1" viewBox="-0.0498162 -5.96091 6.6501 6.1673" width="6.6501pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-111" d="M495 86L479 114C446 82 419 66 409 66C401 66 401 72 406 97C420 166 436 231 453 297C489 435 454 448 428 448C406 448 384 439 354 422C305 394 222 327 161 247H159L183 345C200 415 194 448 173 448C143 448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z"/></g></svg> = 5) to −0.59 (pancreatic cancer, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063904pt" id="M8" height="6.1673pt" version="1.1" viewBox="-0.0498162 -5.96091 6.6501 6.1673" width="6.6501pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-111"/></g></svg> = 2). We concluded that there is an average negative correlation between ADC and SUV in patients with cancer. Higher correlations were found in the brain tumor, cervix carcinoma, and pancreas cancer. However, a larger, prospective study is warranted to validate these findings in different cancer types.

Shengming Deng

Zhifang Wu

Yiwei Wu

Wei Zhang

Jihui Li

Na Dai

Bin Zhang

Jianhua Yan

Meta-Analysis of the Correlation between Apparent Diffusion Coefficient and Standardized Uptake Value in Malignant Disease

Secondary lymphedema accompanied with strong restrictions in quality of life is still major side effects in cancer therapy. Therefore, dedicated diagnostic tools and further investigation of the lymphatic system are crucial to improve lymphedema therapy. In this pilot study, a method for quantitative analysis of the lymphatic system in a rat model by laser ablation (LA) with inductively coupled plasma mass spectrometry imaging (ICP-MSI) is presented. As a possible lymph marker, thulium(III)(1R,4R,7R,10R)-<i>&#x3b1;</i>,<i>&#x3b1;</i>&#x2032;,<i>&#x3b1;</i>&#x2032;&#x2032;,<i>&#x3b1;</i>&#x2032;&#x2032;&#x2032;-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (Tm-DOTMA) is introduced and compared to the clinically used magnetic resonance imaging contrast agent gadolinium(III)2,2&#x2032;,2&#x2032;&#x2032;-(10-((2R,3S)-1,3,4-trihydroxybutan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate (Gd-DO3A-butrol). Gadobutrol functioned as standard contrast media in MRI lymphangiography to detect lymphatic flow qualitatively. Thus, Tm-DOTMA was investigated as lymphatic marker to detect lymphatic flow quantitatively. Both contrast agents were successfully used to visualize the lymphatic flow in successive lymph nodes in LA-ICP-MS due to lower limits of detection compared to MRI. Furthermore, the distribution of contrast agents by multicolored imaging showed accumulation in specific areas (sectors) of the lymph nodes after application of contrast agents in different areas.

Ann-Christin Niehoff

Tim Klasen

Rebecca Schmidt

Daniel Palmes

Cornelius Faber

Uwe Karst

Rebecca Hadrian

Investigating the Lymphatic System by Dual-Color Elemental Mass Spectrometry Imaging

The differential diagnosis between recurrence of gliomas or brain metastases and this phenomenon is important in order to choose the best therapy and predict the prognosis but is still a big problem for physicians. The new emerging MRI, CT, and PET diagnostic modalities still lack sufficient accuracy. Radiolabeled choline and amino acids have been reported to show great tumor specificity. &#x200b;We studied the uptake kinetics of [<sup>18</sup>F]fluoromethyl-choline (FCH) and O-(2-[<sup>18</sup>F]fluoroethyl)-L-tyrosine (FET) by the T98G human glioblastoma cells from 20 to 120&#x2009;min after irradiation either with photons at 2-10-20&#x2009;Gy or with carbon ions at 2&#x2009;Gy (at the National Centre for Oncological Hadrontherapy (CNAO), Pavia, Italy). We also evaluated the cell death and morphology changes induced by radiation treatment. Both FET and FCH are able to trace tumor behavior in terms of higher uptake for increased doses of radiation treatment, due to the upregulation of cells attempts to repair nonlethal damage. Our data suggest that both FCH and FET could be useful to analyze the metabolic pathways of glioblastoma cells before and after radiotherapy. Physicians will have to consider the different kinetics pathways of uptake concerning the two radiopharmaceuticals.

Francesca Pasi

Marco Giovanni Persico

Federica Eleonora Buroni

Carlo Aprile

Marina Hodolic

Franco Corbella

Rosanna Nano

Angelica Facoetti

Lorenzo Lodola

Uptake of <sup>18</sup>F-FET and <sup>18</sup>F-FCH in Human Glioblastoma T98G Cell Line after Irradiation with Photons or Carbon Ions

Accurate imaging of the thymus is essential in the diagnosis and surgical treatment of both neoplastic and nonneoplastic conditions. Imaging of the thymus is a rather complex task, which affects both initial diagnosis and further surgical treatment planning. Imaging techniques include a wide armamentary of possibilities, from the most frequently used computed tomography (CT) to 18-fluorodeoxyglucose positron emission tomography- (18-FDG-PET-) CT and chemical shift magnetic resonance imaging (CS-MRI). In cases where surgical treatment is involved diagnostic imaging is of pivotal importance, not only in distinguishing benign from malignant disease but also in making a way among subtypes of thymic conditions. The article presents a current review of the advantages and backdrops of different imaging techniques used in the diagnosis of benign and malignant thymic conditions, with emphasis on differential imaging of thymic hyperplasia (TH), ectopic thymic tissue (ETT), and thymic epithelial tumors (TETs), with special attention to the importance of MR imaging according to the new TNM classification of thymic epithelial tumors.

Aurel Ottlakan

Bernadett Borda

Zita Morvay

Aniko Maraz

Jozsef Furak

The Effect of Diagnostic Imaging on Surgical Treatment Planning in Diseases of the Thymus

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<p><em>Contrast Media &amp; Molecular Imaging</em>&nbsp;is an exciting journal in the area of contrast agents and molecular imaging, covering all areas of imaging technologies with a special emphasis on&nbsp;MRI and PET.</p>


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<p>Chief Editor, Professor Zimmer, focuses&nbsp;on the development and use of PET radiotracers for new applications of PET/MRI imaging in neuroscience and pharmacology.</p>


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Contrast Media & Molecular Imaging is an exciting journal in the area of contrast agents and molecular imaging, covering all areas of imaging technologies with a special emphasis on MRI and PET.

Contrast Media & Molecular Imaging